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ධՁࢦඪ࡞੒ࣄ‫ۀ‬࠶ੜҩྍ৹ࠪ 8( ใࠂॻ















࠶ੜҩྍ৹ࠪ 8( ࠲௕඿দҩՊେֶ ੔‫֎ܗ‬Պֶߨ࠲দࢁ ޾߂

┠ḟI.

ḟୡ௦་⒪ᶵჾ࣭෌⏕་⒪➼〇ရホ౯ᣦᶆసᡂ஦ᴗ෌⏕་⒪ᑂᰝ WG

   ௧࿴ඖᖺᗘጤဨྡ⡙ ·················································································· 1II.

௧࿴ඖᖺᗘ఍㆟㆟஦ᴫせ ·············································································· 3III. ࣄࢺ㸦ྠ✀㸧iPS㸦ᵝ㸧⣽⬊ຍᕤ〇ရࢆ⏝࠸ࡓளᛴᛶᮇ⬨㧊ᦆയ㸦እയᛶ㸧ࡢ἞⒪࡟
㛵ࡍࡿホ౯ᣦᶆ㸦᱌㸧 ················································································11
IV.

ㄪᰝ஦㡯

1. ⥲ᣓ                          ᯇᒣ ᖾᘯ ·········· 29
2. ளᛴᛶᮇ⬨㧊ᦆയ࣭෌⏕἞⒪⏝ iPS ⣽⬊⏤᮶⚄⤒๓㥑⣽⬊  㔠ᮧ ⡿༤ ·········· 31
3. ⏝ㄒࡢᐃ⩏㸦ヲ⣽㸧     ᅧᗓ⏣ṇ㞝 ⥴᪉ᚭ Ἴ࿅ᾈᏕ Ώ㎶㞞ᙪ ·········· 33
V.

ཧ⪃㈨ᩱ

1. ᖹᡂ 24 ᖺ 9 ᭶ 7 ᪥௜⸆㣗Ⓨ 0907 ➨ 5 ྕཌ⏕ປാ┬་⸆㣗ရᒁ㛗㏻▱
䛂䝠䝖䠄ྠ✀䠅iPS䠄ᵝ䠅⣽⬊ຍᕤ་⸆ရ➼䛾ရ㉁ཬ䜃Ᏻ඲ᛶ䛾☜ಖ䛻㛵䛩䜛ᣦ㔪䛃 ·········· 37
2. ௧࿴ඖᖺ 5 ᭶ 8 ᪥௜⸆⏕⸆ᑂⓎ 0508 ➨ 1 ྕ⸆⏕ᶵᑂⓎ 0508 ➨ 1 ྕཌ⏕ປാ┬་⸆䞉⏕ά⾨⏕ᒁ་⸆ရᑂᰝ⟶⌮ㄢ㛗㏻▱䛂ᛴᛶᮇ⬨㧊ᦆയ䛾἞⒪䜢┠ⓗ䛸䛧䛯་⸆ရ➼䛾⮫ᗋホ౯䛻㛵䛩䜛䜺䜲䝗䝷䜲䞁䛃·········· 59
3. ௧࿴ඖᖺ 6 ᭶ 27 ᪥௜⸆⏕ᶵᑂⓎ 0627 ➨ 1 ྕཌ⏕ປാ┬་⸆䞉⏕ά⾨⏕ᒁ་⒪ᶵჾᑂᰝ⟶⌮ㄢ㛗㏻▱
䛂䝠䝖⣽⬊ຍᕤ〇ရ䛾ᮍศ໬ከ⬟ᛶᖿ⣽⬊䞉ᙧ㉁㌿᥮⣽⬊᳨ฟヨ㦂䚸㐀⭘⒆ᛶヨ㦂ཬ䜃㑇ఏⓗᏳᐃᛶホ౯䛻㛵䛩䜛␃ពⅬ䛃····································································· 76

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@Ƒ]ƒ ġĠ ĝ ĝ ĝ Y^aĝ䝠䝖⣽⬊⏤᮶⚄⤒๓㥑⣽⬊ளᛴᛶᮇ⬨㧊ᦆയ䞉෌⏕἞⒪⏝iPS⣽⬊⏤᮶⚄⤒๓㥑⣽⬊䛆〇㐀䞉ရ㉁⟶⌮ἲ䛇ᇶ♏◊✲㛤Ⓨẁ㝵䠄┠ⓗ䠅䞉iPS⣽⬊䛛䜙䛾ຠ⋡ⓗ⚄⤒ศ໬ㄏᑟᢏ⾡䛾㑅ᐃ䞉ᮍศ໬⣽⬊ṧ␃䝸䝇䜽䜢᭱኱㝈పῶ䛧䛯ศ໬ㄏᑟἲ䛾㑅ᐃ䞉㐀⭘⒆⬟䝸䝇䜽䜢᭱኱㝈పῶ䛧䛯ศ໬ㄏᑟἲ䛾㑅ᐃᇶ♏◊✲䝺䝧䝹䛷䛾POCྲྀᚓ
           ᐇ⏝໬◊✲㛤Ⓨẁ㝵     䠄┠ⓗ䠅䞉⏕≀⏤᮶ཎᩱᇶ‽ᑐᛂ䞉᭱⤊〇ရつ᱁䞉〇㐀ᕤ⛬⟶⌮᪉ἲ䛾☜❧䞉ရ㉁⟶⌮᪉ἲ䛾☜❧䠄⊂䠅ᅜ❧⑓㝔ᶵᵓ኱㜰་⒪䝉䞁䝍䞊1⮫ᗋ◊✲䝉䞁䝍䞊䞉ඛ㐍་⒪◊✲㛤Ⓨ䚸2⬻⚄⤒እ⛉
3៞᠕⩏ሿ኱Ꮫ་Ꮫ㒊䞉⏕⌮Ꮫᩍᐊ㔠ᮧ⡿༤1,2,3

㠀⮫ᗋPOCྲྀᚓ䝠䝖iPS⣽⬊䛛䜙䛾⚄⤒๓㥑⣽⬊〇㐀ᕤ⛬䛾᭱㐺໬⚄⤒ศ໬ㄏᑟᕤ⛬䛾᭱㐺໬
Dual SMADἲ䜢⏝䛔䛯ຠ⋡䛾Ⰻ䛔⚄⤒ศ໬ㄏᑟἲ

య⣽⬊
OCT4

య⣽⬊
䝸䝥䝻䜾䝷䝭䞁䜾

SOX2

KLF4

C-MYC

iPS⣽⬊
᥋╔ᇵ㣴
䠄PLO/LAM dish)

BMP⤒㊰㜼ᐖ๣ 䠄Noggin, Dorsomorphin➼)
Activin/Nodal⤒㊰㜼ᐖ๣䠄SB431542➼䠅
FGF2㝖ཤ

⣽⬊จ㞟ሢᙧᡂ䠄⬇ᵝయ䠅⚄⤒ୖ⓶๓㥑⣽⬊ 䠄 䠖 䠅

endoderm

rosetteᙧᡂ
EGF+FGF2
EGF+FGF2

lt-NES

mesoderm

DAPI/ZO-1⚄⤒๓㥑⣽⬊ 䠄 䠖 䠅

EGF+FGF2

EGF+FGF2䠄㔠ᮧ䜋䛛. Clinical Neuroscience 36, 299-303,2018)(Fukusumi et al., Stem Cell Int, 7235757, 2016)

in vivo㐀⭘⒆ᛶホ౯⣽⬊จ㞟ሢᙧᡂἲ䠄⚄⤒䝻䝊䝑䝖ᙧᡂἲ䠄 

䠅
䠅

἞⒪⏝⣽⬊䞉〇㐀ရ㉁⟶⌮䠍䠊ཎᮦᩱ䛚䜘䜃〇㐀㛵㐃≀㉁  䞉䝠䝖iPS⣽⬊䠖ி㒔኱ᏛCiRAస〇䛾HLA䝩䝰䝠䝖iPS⣽⬊䝇䝖䝑䜽⬻ෆ⛣᳜   䞉ヨ⸆䞉㈨ᮦ䠖㑅ᐃ䚸⏕≀⏤᮶ཎᩱᇶ‽䠄1x106 /⥺᮲య∦ഃ䠅䠎䠊〇㐀ᕤ⛬⟶⌮  䞉〇㐀᪉ἲ䛾⟇ᐃ   䞉ᕤ⛬⟶⌮ᣦᶆ䛾⟇ᐃ   䞉䝻䝑䝖ᵓᡂ䚸〇㐀䝇䜿䞊䝹⟇ᐃᦆയ⬨㧊⛣᳜
䠄5x105 /ᦆയ⬨㧊䠅䠏䠊ရ㉁⟶⌮ἲ  䞉᭱⤊〇ရ䠄≉ᐃ⣽⬊ຍᕤ≀䠅䛾ᙧែ䚸ໟ⿦   䞉᭱⤊〇ရ䛾ရ㉁つ᱁⛣᳜ᚋ䠏ࠥ12䞄᭶⤌⧊Ꮫⓗホ౯ᦆയ⬨㧊⛣᳜      ⣽⬊ᩘ୪䜃䛻⏕Ꮡ⋡         ☜ㄆヨ㦂         ⣧ᗘヨ㦂         ⣽⬊⏤᮶䛾┠ⓗእ⏕⌮άᛶ≀㉁䛻㛵䛩䜛ヨ㦂         〇㐀ᕤ⛬⏤᮶୙⣧≀ヨ㦂         ↓⳦ヨ㦂ཬ䜃䝬䜲䝁䝥䝷䝈䝬ྰᐃヨ㦂         䜶䞁䝗䝖䜻䝅䞁ヨ㦂         䜴䜲䝹䝇ヨ㦂         ຠ⬟ヨ㦂         ຊ౯ヨ㦂         ຊᏛⓗ㐺ྜᛶヨ㦂    䞉୰㛫〇ရ䛾ရ㉁☜ㄆἲ⬻ෆ⛣᳜

NR-NSPCs

EB-NSPCsᰁⰍయ᰾ᆺ᳨ᰝ

⛣᳜∦䝃䜲䝈ᐃ㔞ホ౯෌⏕་⒪䛾Ᏻ඲ᛶ䛾☜ಖ➼䛻㛵䛩䜛ἲᚊ䝠䝖䠄ྠ✀䠅iPS䠄ᵝ䠅⣽⬊ຍᕤ་⸆ရ➼䛾ရ㉁ཬ䜃Ᏻ඲ᛶ䛾☜ಖ䛻㛵䛩䜛ᣦ㔪

(Sugai et al., Mol Brain 8, 85, 2016)㸫㸫

⮫ᗋヨ㦂⏝䝠䝖iPS⣽⬊⏤᮶⚄⤒๓㥑⣽⬊⮫ᗋヨ㦂⏝䝠䝖iPS⣽⬊⏤᮶⚄⤒๓㥑⣽⬊䛆᭱⤊〇ရ ရ㉁つ᱁䛇1"$⣽⬊
䠄෾⤖⣽⬊䠅 1"$⣽⬊ᦙධᕤ⛬ヨ㦂㡯┠⣽⬊ᩘ䛺䜙䜃䛻⏕Ꮡ⋡ᕤ⛬ෆရ㉁⟶⌮ヨ㦂

 1"$⣽⬊ᇵ㣴ᕤ⛬1"$⣽⬊
䠄⏕⣽⬊䠅☜ㄆヨ㦂㔜せ୰㛫య
䠄ศ໬ㄏᑟ㛤ጞ๓䠅 ⚄⤒ศ໬ㄏᑟᕤ⛬䠄┠ⓗ⣽⬊䛷䛒䜛䛣䛸䛾☜ㄆ䠅ᕤ⛬ෆရ㉁⟶⌮ヨ㦂⬇ᵝయ㔜せ୰㛫య
䠄୰㛫⬇ᵝయ䠅ᕤ⛬ෆရ㉁⟶⌮ヨ㦂neurosphereᙧែホ౯ヨ㦂⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅㢧ᚤ㙾ほᐹἲ

㑇ఏᏊⓎ⌧ゎᯒ⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅TaqMan PCRἲ⣽⬊⾲㠃䝬䞊䜹䞊Ⓨ⌧ゎᯒ⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅⣽⬊ෆ䝬䞊䜹䞊ศᏊⓎ⌧ゎᯒ⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅㑇ఏᏊⓎ⌧ゎᯒ⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅⣽⬊⾲㠃䝬䞊䜹䞊Ⓨ⌧ゎᯒ⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅⣽⬊ෆ䝬䞊䜹䞊ศᏊⓎ⌧ゎᯒ⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅ᡠ䛧ᇵ㣴ゎᯒ

⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅ᰁⰍయ᰾ᆺゎᯒ⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅య⣽⬊䝁䝢䞊ᩘ ゎᯒᕤ⛬ෆရ㉁⟶⌮ヨ㦂↓⳦ヨ㦂 ᭱⤊〇ရస〇ᕤ⛬᭱⤊〇ရ⣽⬊⏤᮶⚄⤒๓㥑⣽⬊䠅䠄ゎ෾䞉ㄪ〇䠅

1E+13
1E+12

1E+09
100000000

䜼䝮䝄ᰁⰍゎᯒἲ䝯䞁䝤䝷䞁䝣䜱䝹䝍䞊ἲ䚸䝞䜽䝔䜰䝷䞊䝖ἲ᪥ᮏ⸆ᒁ᪉䠄እ㒊ጤク᳨ᰝ䠅䜹䜲䝛䝔䜱䝑䜽ẚ⃮ἲ⚄⤒๓㥑⣽⬊ 䠄෾⤖〇ရ䠅᪥ᮏ⸆ᒁ᪉ 䠄እ㒊ጤク᳨ᰝ䠅ᇵ㣴ୖΎ    䠄෾⤖๓〇ရ䠅᰾㓟ቑᖜἲ⚄⤒๓㥑⣽⬊ 䠄෾⤖〇ရ䠅᪥ᮏ⸆ᒁ᪉䠄Aἲ䚸Cἲ䠅 䠄እ㒊ጤク᳨ᰝ䠅⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅䠄┠ⓗ⣽⬊䛸䛧䛶䛾≉ᛶホ౯䠅䠄㔠ᮧ䚸ᒸ㔝䝞䜲䜸䝻䝆䜽䝇䛾㛤Ⓨ䛸ရ㉁䞉Ᏻ඲ᛶ☜ಖ᰾㓟ቑᖜἲ 䠄እ㒊ጤク᳨ᰝ䠅⣽⬊ศ໬ㄏᑟἲ䞉⺯ග⣽⬊ච␿ᰁⰍἲ
䠄⚄⤒⣽⬊䝬䞊䜹䞊䚸䜾䝸䜰⣽⬊䝬䞊䜹䞊䠅⣽⬊ศ໬ㄏᑟἲ䞉⺯ග⣽⬊ච␿ᰁⰍἲ
䠄ᡂ⇍⚄⤒䝬䞊䜹䞊䠅ရ㉁⟶⌮ୖ䛾᳨ウㄢ㢟䠍䠊䛹䛾᳨ᰝ㡯┠䠄䝬䞊䜹䞊䠅䜢᳨ᰝ䛩䜉䛝䛛䚹☜ㄆヨ㦂䠖෌⌧ᛶ䜢䜒䛳䛶┠ⓗ⣽⬊䜢ྠᐃ䛩䜛⣧ᗘヨ㦂䠖┠ⓗእ⣽⬊䠄ᮍศ໬⣽⬊䠅䜢☜ᐇ䛻ྠᐃ䛩䜛ಸ

䠎䠊䛹䛾᳨ᰝ᪉ἲ䜢᥇⏝䛩䜛䜉䛝䛛䚹ಸ
ಸ

᳨ᰝឤᗘ᳨ᰝ䛾෌⌧ᛶ
᳨ᰝᡭᢏ䛾」㞧ᛶ᳨ᰝ䛻౑⏝䛩䜛⣽⬊ᩘ

⬇
ᵝ
య
ᙧ
ᡂ
㛤
ጞ

㑇ఏᏊⓎ⌧ゎᯒ⣽⬊⾲㠃䝬䞊䜹䞊Ⓨ⌧ゎᯒ⣽⬊ෆ䝬䞊䜹䞊Ⓨ⌧ゎᯒᰁⰍయゎᯒ
䝀䝜䝮ゎᯒ

䠏䠊ຠ⬟ຠᯝ䜢䝃䝹䝀䞊䝖䛩䜛ရ㉁ᣦᶆ䛿ఱ䛛䚹10000000ᡠ䛧ᇵ㣴ヨ㦂ἲᇵ㣴ୖΎ    䠄෾⤖๓〇ရ䠅⚄⤒ศ໬⬟ヨ㦂

ຠ⬟ヨ㦂

1E+11
1E+10

ᐃヨ㦂

⚄⤒๓㥑⣽⬊ 䠄෾⤖〇ရ䠅

1000000 ᇶ♏◊✲┠ⓗ䛷䛾⥙⨶ⓗ᳨ᰝ䛷䛿䛺䛟䚸⮫ᗋ⏝⣽⬊䛾ရ㉁ヨ㦂䛸䛧䛶䝫䜲䞁䝖䜢⤠䛳䛯䚸ᚲせ䛛䛴༑ศ䛺つ᱁䛾タᐃ䛸᳨ᰝἲ䛾㑅ᐃ ἲ௧㡰Ᏺ䠄෌⏕་⒪䛾Ᏻ඲ᛶ䛾☜ಖ➼䛻㛵䛩䜛ἲᚊ䚸෌⏕་⒪➼〇ရ䛾〇㐀⟶⌮ཬ䜃ရ㉁⟶⌮䛾ᇶ‽䛻㛵䛩䜛┬௧䛆GCTP┬௧䛇䠅

P䠐⤊஢᫬

100000
10000

0
3
6
9
12
15
18
21
24
27
30
33
36
39
42
45
48
51
54
57
60
63
66
69
72
75
78
81
84
87
90
93
96
99
102
105
108

⣼ィ⣽⬊ᩘ

ಸ

FCMἲ䠖䠄ከ⬟ᛶᖿ⣽⬊䝬䞊䜹䞊䠅䝬䜲䜽䝻䜰䝺䜲ἲ䜴䜲䝹䝇ྰᐃ᳨ᰝ

⣽⬊ቑṪ᭤⥺ಸ

FCMἲ䠖䠄ከ⬟ᛶᖿ⣽⬊䝬䞊䜹䞊䠅⺯ග⣽⬊ච␿ᰁⰍἲ䠖䠄ከ⬟ᛶᖿ⣽⬊䝬䞊䜹䞊䠅⚄⤒๓㥑⣽⬊ 䠄෾⤖〇ရ䠅෾⤖〇ရつ᱁ヨ㦂

1E+15

 㽢
 㽢
RWMH09s01
 㽢
⣽⬊C
㽢
Ff-I01
⣽⬊D
 㽢
⣽⬊E
1210B2⺯ග⣽⬊ච␿ᰁⰍἲ䠖䠄⚄⤒๓㥑⣽⬊䝬䞊䜹䞊䠅ᇵ㣴ୖΎ    䠄෾⤖๓〇ရ䠅䝬䜲䝁䝥䝷䝈䝬ྰᐃヨ㦂〇㐀ᕤ⛬⟶⌮

⣽⬊A

FCMἲ䠖䠄⚄⤒๓㥑⣽⬊䝬䞊䜹䞊䠅
FCMἲ䠖䠄⚄⤒๓㥑⣽⬊䝬䞊䜹䞊䠅
TaqMan PCRἲ䠖䠄ከ⬟ᛶᖿ⣽⬊䝬䞊䜹䞊䠅⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅෾⤖๓〇ရつ᱁ヨ㦂᭱⤊ᠱ⃮ရつ᱁ヨ㦂YZWJs513⣽⬊B䜶䞁䝗䝖䜻䝅䞁

ឤᰁ⑕ヨ㦂

䠄෾⤖䞉ಖ⟶䠅

Ff-WJ14s01

⺯ගᰁⰍἲG䝞䞁䝗ศᰁἲ

㔜せ୰㛫య
䠄୰㛫⥅௦⣽⬊䠅

1E+14

⺯ගᰁⰍἲ

⚄⤒๓㥑⣽⬊ 䠄෾⤖〇ရ䠅䠄┠ⓗእ⣽⬊䛾ྵ᭷⋡ホ౯䠅

䝠䝖1"$⣽⬊⏤᮶⚄⤒๓㥑⣽⬊⣽⬊ᢞ୚ᾮ䠄᭱⤊ᠱ⃮ရ䠅䠄䝠䝖 ⣽⬊⏤᮶⚄⤒๓㥑⣽⬊䠅ヨ㦂᪉ἲ⚄⤒๓㥑⣽⬊ 䠄෾⤖๓〇ရ䠅⣧ᗘヨ㦂 ⚄⤒๓㥑⣽⬊ᇵ㣴ᕤ⛬

䠄䝠䝖

ヨ㦂᳨య

Days in vitro㸫㸫

Řƻ7ÞƍǺƹƀǻ 








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ࣄࢺ⏤᮶ࡢ⣽⬊࣭⤌⧊ࢆຍᕤࡋࡓ་⸆ရཪࡣ་⒪ᶵჾࡢရ㉁ཬࡧᏳ඲ᛶࢆ☜ಖࡍࡿࡓࡵࡢᇶᮏⓗ࡞ᢏ⾡せ௳࡟ࡘ࠸࡚ࡣࠊᖹᡂᖺ㸰᭶㸶᪥௜ࡅ⸆㣗Ⓨ➨
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ࡣࡌࡵ࡟

㸯㸬 ᮏᣦ㔪ࡣࠊࣄࢺ⏤᮶ࡢேᕤከ⬟ᛶᖿ⣽⬊㸦& ⣽⬊㸧ཪࡣேᕤከ⬟ᛶᖿ⣽⬊ᵝ⣽⬊㸦& ᵝ⣽⬊㸧ࡢ࠺ࡕࠊྠ✀⏤᮶ & ⣽⬊ཪࡣ & ᵝ⣽⬊㸦⮬ᕫ⏤᮶ & ⣽⬊ཪࡣ &ᵝ⣽⬊ࢆ㝖ࡃ㸧ࢆຍᕤࡋࡓ་⸆ရཪࡣ་⒪ᶵჾ௨ୗࠕࣄࢺྠ✀& 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࠖ࡜࠸࠺ࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖࡢࡓࡵࡢᇶᮏⓗ࡞ᢏ⾡せ௳࡟ࡘ࠸࡚ᐃࡵ
ࡿࡶࡢ࡛࠶ࡿࠋࡋ࠿ࡋ࡞ࡀࡽࠊࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡣࠊࣄࢺయ⣽⬊ࡼࡾேⅭⓗ࡟స〇ࡉࢀࡓྛ✀ & 㸦ᵝ㸧⣽⬊ࢆேⅭⓗ࡟ศ໬ㄏᑟࡋࠊᚓࡽࢀࡓ≉ᐃࡢ⣽⬊ࢆࡑࡢࡲࡲ฼⏝ࠊ࠶ࡿ࠸ࡣࡉࡽ࡟ຍᕤࡍࡿࡇ࡜࡟ࡼࡾ〇㐀ࡉࢀࡿࡓࡵࠊࡑࡢ〇㐀᪉ἲࠊ୰㛫〇ရࡸ┠ⓗ⣽⬊ࡢ✀㢮ཬࡧ≉ᛶࠊ⮫ᗋୖࡢ㐺⏝ἲࡣከ✀ከᵝ࡛࠶ࡾࠊࡲࡓࠊᮏศ
㔝࡟࠾ࡅࡿ⛉Ꮫⓗ㐍Ṍࡸ⤒㦂ࡢ⵳✚ࡣ᪥㐍᭶Ṍ࡛࠶ࡿࠋᮏᣦ㔪ࢆ୍ᚊ࡟㐺⏝ࡋࡓࡾࠊᮏᣦ㔪ࡢෆᐜࡀᚲせ஦㡯ࡍ࡭࡚ࢆໟྵࡋ࡚࠸ࡿ࡜ࡳ࡞ࡋࡓࡾࡍࡿࡇ࡜ࡀᚲࡎࡋࡶ㐺ษ࡛࡞࠸ሙྜࡶ࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊಶࠎࡢ་⸆ရ➼࡟ࡘ࠸࡚ࡢヨ㦂ࡢᐇ᪋ࡸホ౯࡟㝿ࡋ࡚ࡣᮏᣦ㔪ࡢ┠ⓗࢆ㋃ࡲ࠼ࠊࡑࡢ᫬ⅬࡢᏛၥࡢ㐍Ṍࢆ཯ᫎࡋࡓྜ⌮ⓗ᰿ᣐ࡟ᇶ࡙
ࡁࠊࢣ࣮ࢫ࣭ࣂ࢖࣭ࢣ࣮ࢫ࡛ᰂ㌾࡟ᑐᛂࡍࡿࡇ࡜ࡀᚲせ࡛࠶ࡿࡇ࡜ࠋ㸰㸬 ⸆஦ᡓ␎┦ㄯ࠶ࡿ࠸ࡣ἞㦂┦ㄯ࡟࠾ࡅࡿࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢ἞㦂ࢆ㛤ጞࡍࡿ࡟ᙜࡓࡗ࡚ࡢᇶᮏⓗ␃ពⅬࡣࠊᙜヱ〇ရ࡟ࣄࢺ࡬ࡢ㐺⏝࡟ࡼࡾᨭ㞀࡜࡞ࡿရ㉁ཬࡧᏳ඲ᛶୖࡢ᫂ࡽ࠿࡞ၥ㢟ࡀᏑᅾࡍࡿ࠿ྰ࠿ࠊ⮫ᗋ࡛ᚓࡽࢀࡓ▱ぢ࡜ࡢ㛵ಀᛶࢆ↷ྜ࡛ࡁࡿ⛬ᗘ࡟ရ㉁≉ᛶࡀᢕᥱࡉࢀࠊࡑࡢ୍ᐃ⠊ᅖࡢᜏᖖᛶࡀ☜ಖࡉࢀ࡚࠸ࡿ࠿ྰ
࠿ࢆ☜ㄆࡍࡿࡇ࡜࡟࠶ࡿࠋࡑࡢ㝿ࠊ᫂ࡽ࠿࡟᝿ᐃࡉࢀࡿ〇ရࡢࣜࢫࢡࢆ⌧ᅾࡢᏛၥ࣭
ᢏ⾡ࢆ㥑౑ࡋ࡚᤼㝖ࡋࠊࡑࡢ⛉Ꮫⓗጇᙜᛶࢆ᫂ࡽ࠿࡟ࡋࡓୖ࡛ࠊ࡞࠾ṧࡿࠕᮍ▱ࡢࣜࢫࢡࠖ࡜ࠊ㔜⠜࡛⏕࿨ࢆ⬣࠿ࡍ⑌ᝈࠊ㌟యࡢᶵ⬟ࢆⴭࡋࡃᦆ࡞࠺⑌ᝈࠊ㌟యࡢᶵ⬟ࡸᙧែࢆ୍ᐃ⛬ᗘᦆ࡞࠺ࡇ࡜࡟ࡼࡾ  ࢆⴭࡋࡃᦆ࡞࠺⑌ᝈ࡞࡝࡟⨯ᝈࡋࠊᚑ᮶ࡢ἞⒪ἲ࡛ࡣ㝈⏺ࡀ࠶ࡾࠊඞ᭹࡛ࡁ࡞࠸ᝈ⪅ࡀࠕ᪂ࡓ࡞἞⒪ᶵ఍ࢆኻ࠺ࡇ࡜࡟ࡼࡾ⿕ࡿ࠿ࡶࡋࢀ࡞࠸ࣜࢫࢡࠖ࡜ࡢࣜࢫࢡࡢ኱ᑠࢆ຺᱌ࡋࠊ࠿ࡘࠊࡇࢀࡽࡍ࡭࡚ࡢ᝟ሗࢆ㛤♧ࡋࡓୖ࡛ᝈ⪅ࡢ⮬ᕫỴᐃᶒ࡟ጤࡡࡿ࡜࠸࠺どⅬࢆᣢࡘࡇ࡜ࠊࡍ࡞ࢃࡕࠊࣜࢫࢡ࣭ᮇᚅࡉࢀ
ࡿ࣋ࢿࣇ࢕ࢵࢺࡢ᝟ሗࢆ㛤♧ࡋࡓୖ࡛ࠊ἞㦂࡟ධࡿ࠿࡝࠺࠿ࡢពᛮỴᐃࡣᝈ⪅ࡀ⾜࠺࡜࠸࠺どⅬࢆධࢀ࡚ホ౯ࡍࡿࡇ࡜ࡶ㔜せ࡛࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊ἞㦂㛤ጞࡢሙྜࠊࡑࡢ
ᒆฟ࡟ᙜࡓࡗ࡚ῧ௜ࡍࡿ࡭ࡁ㈨ᩱ࡟ࡘ࠸࡚ᮏᣦ㔪࡟♧ࡉࢀࡓせ௳ࡸෆᐜࢆࡍ࡭࡚඘
ࡓࡍࡇ࡜ࢆᚲࡎࡋࡶồࡵ࡚࠸ࡿヂ࡛ࡣ࡞࠸ࠋ〇㐀㈍኎ᢎㄆ⏦ㄳ᫬࡟࠾ࡅࡿရ㉁ཬࡧᏳ
඲ᛶࡢ☜ಖࡢࡓࡵࡢ㈨ᩱࡣ἞㦂ࡢ㐍⾜࡜࡜ࡶ࡟ᮏᣦ㔪࡟ἢࡗ࡚඘ᐇᩚഛࡉࢀࡿࡇ࡜
ࢆ๓ᥦ࡟ࠊ἞㦂㛤ጞ᫬Ⅼ࡛ࡑࡢ㊃᪨࡟㐺࠺᮲௳ࢆ඘ࡓࡋࠊྜ⌮ⓗ࡟సᡂࡉࢀࡓ㐺ษ࡞㈨ᩱࢆᥦฟࡍࡿࡇ࡜ࠋ   ࡲࡓࠊ἞㦂㛤ጞ࡟ᚲせ࡜ࡉࢀࡿ㈨ᩱࡢ⠊ᅖཬࡧ⛬ᗘ࡟ࡘ࠸࡚ࡣࠊᙜヱ〇ရࡢ⏤᮶ࠊᑐ㇟⑌ᝈࠊᑐ㇟ᝈ⪅ࠊ㐺⏝㒊఩ࠊ㐺⏝᪉ἲཬࡧຍᕤ᪉ἲ➼࡟ࡼࡾ␗࡞ࡾࠊᮏᣦ㔪࡛ࡣලయⓗ࡟᫂ࡽ࠿࡛࡞࠸ࡇ࡜ࡶᑡ࡞ࡃ࡞࠸ࡢ࡛ࠊಶู࡟⊂❧⾜ᨻἲே་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ࡟┦ㄯࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ
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࠾ࡾࠊᚲࡎࡋࡶᖖ࡟ྠ୍㸦᭱㧗㸧Ỉ‽࡛ࡢゎ㔘ࠊ㐠⏝ࢆồࡵ࡚࠸ࡿヂ࡛ࡣ࡞࠸ࠋࡇ
ࡢ㊃᪨ࢆ㋃ࡲ࠼ࠊ⏦ㄳ⪅ࡣࠊ⪃៖ࡋࡓ⫼ᬒࠊ㑅ᢥࠊ㐺⏝ࠊཬࡧホ౯ࡋࡓෆᐜ࡜⛬ᗘࡀࡑࢀࡒࢀࡢ┠ⓗ࡟┦ᛂࡋࡃࠊ⛉Ꮫⓗྜ⌮ᛶ࠿ࡽࡳ࡚ጇᙜ࡛࠶ࡿࡇ࡜ࢆ᫂ࡽ࠿࡟ࡍ
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┠ḟ➨㸯❶ ⥲๎㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 ➨㸯 ┠ⓗ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 ➨㸰 ᐃ⩏㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 ➨㸰❶ 〇㐀᪉ἲ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 ➨㸯 ཎᮦᩱཬࡧ〇㐀㛵㐃≀㉁㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸯 & 㸦ᵝ㸧⣽⬊సᡂࡢཎᮦᩱ࡜࡞ࡿࣄࢺయ⣽⬊㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ㉳※ཬࡧ⏤᮶ࠊ㑅ᢥ⌮⏤㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ཎᮦᩱ࡜࡞ࡿ⣽⬊࣭⤌⧊ࡢ≉ᛶ࡜㐺᱁ᛶ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃   ࢻࢼ࣮࡟㛵ࡍࡿグ㘓㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⣽⬊࣭⤌⧊ࡢ᥇ྲྀ࣭ಖᏑ࣭㐠ᦙ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸰 ┠ⓗ࡜ࡍࡿ⣽⬊࣭⤌⧊௨እࡢཎᮦᩱཬࡧ〇㐀㛵㐃≀㉁㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 ⣽⬊ࡢᇵ㣴ࢆ⾜࠺ሙྜ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㠀⣽⬊ᡂศ࡜⤌ࡳྜࢃࡏࡿሙྜ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⣽⬊࡟㑇ఏᏊᕤᏛⓗᨵኚࢆຍ࠼ࡿሙྜ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⣽⬊࡟ࢱࣥࣃࢡ㉁ࢆᑟධࡍࡿሙྜ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⸆๣➼ࡢฎ⌮࡟ࡼࡾ⣽⬊ࡢึᮇ໬ࠊ⬺ศ໬ཪࡣศ໬ㄏᑟࢆ⾜࠺ሙྜ㺃㺃㺃㺃㺃㺃㺃㺃  ≀⌮ⓗ᪉ἲ࡟ࡼࡾ⣽⬊ࡢึᮇ໬ࠊ⬺ศ໬ཪࡣศ໬ㄏᑟࢆ⾜࠺ሙྜ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ࢥࣥࣅࢿ࣮ࢩࣙࣥ࡟ࡼࡾ⣽⬊ࡢึᮇ໬ࠊ⬺ศ໬ཪࡣศ໬ㄏᑟࢆ⾜࠺ሙྜ㺃㺃㸱 ࣄࢺ & 㸦ᵝ㸧⣽⬊ࡢᶞ❧㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㸲 ࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴࡢಖᏑཬࡧ㐠ᦙ᪉ἲ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸳 グ㘓ࡢసᡂཬࡧಖ⟶᪉ἲ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃➨㸰 〇㐀ᕤ⛬㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㸯 ࣟࢵࢺᵓᡂࡢ᭷↓࡜ࣟࢵࢺࡢつᐃ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸰 〇㐀᪉ἲ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ཷධ᳨ᰝ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⣽⳦ࠊ┿⳦ཬࡧ࢘࢖ࣝࢫ➼ࡢ୙ά໬࣭㝖ཤ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⤌⧊ࡢ⣽ษࠊ⣽⬊ࡢศ㞳ࠊ≉ᐃ⣽⬊ࡢ༢㞳➼㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴࡢᶞ❧㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ࣄࢺ & 㸦ᵝ㸧⣽⬊⏤᮶ࡢ୰㛫⣽⬊ᰴࡢᶞ❧㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ᭱⤊〇ရࡢᵓᡂせ⣲࡜࡞ࡿ⣽⬊ࡢసᡂ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⣽⬊ࡢࣂࣥࢡ໬㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 〇㐀ᕤ⛬୰ࡢྲྀࡾ㐪࠼ཬࡧࢡࣟࢫࢥࣥࢱ࣑ࢿ࣮ࢩࣙࣥ㜵Ṇᑐ⟇㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸱 ᭱⤊〇ရࡢᵓᡂせ⣲࡜࡞ࡿ⣽⬊ࡢ≉ᛶゎᯒ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸲 ᭱⤊〇ရࡢᙧែࠊໟ⿦㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸳 〇ရࡢಖᏑཬࡧ㐠ᦙ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸴 〇㐀᪉ἲࡢᜏᖖᛶ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸵 〇㐀᪉ἲࡢኚ᭦㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 
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➨㸱 ᭱⤊〇ရࡢရ㉁⟶⌮㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸯 ⥲ㄽ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 㸰 ᭱⤊〇ရࡢရ㉁⟶⌮ἲ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⣽⬊ᩘ୪ࡧ࡟⏕Ꮡ⋡㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ☜ㄆヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⣽⬊ࡢ⣧ᗘヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ⣽⬊⏤᮶ࡢ┠ⓗእ⏕⌮άᛶ≀㉁࡟㛵ࡍࡿヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  〇㐀ᕤ⛬⏤᮶୙⣧≀ヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ↓⳦ヨ㦂ཬࡧ࣐࢖ࢥࣉࣛࢬ࣐ྰᐃヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃  ࢚ࣥࢻࢺ࢟ࢩࣥヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 ࢘࢖ࣝࢫヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 ຠ⬟ヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 ຊ౯ヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃 ຊᏛⓗ㐺ྜᛶヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃➨㸱❶ ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢᏳᐃᛶ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃➨㸲❶ ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢ㠀⮫ᗋᏳ඲ᛶヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃➨㸳❶ ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢຠຊཪࡣᛶ⬟ࢆ⿬௜ࡅࡿヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃➨㸴❶ ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢయෆືែ㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃➨㸵❶ ⮫ᗋヨ㦂㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃㺃
㸫㸫

➨㸯❶ ⥲๎➨㸯 ┠ⓗᮏᣦ㔪ࡣࠊࣄࢺྠ✀& 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖࡢࡓࡵࡢᇶᮏⓗ࡞ᢏ⾡せ௳࡟ࡘ࠸࡚ᐃࡵࡿࡶࡢ࡛࠶ࡿࠋ➨㸰 ᐃ⩏ᮏᣦ㔪࡟࠾ࡅࡿ⏝ㄒࡢᐃ⩏ࡣ௨ୗࡢ࡜࠾ࡾ࡜ࡍࡿࠋ㸯 ࠕࣄࢺேᕤከ⬟ᛶᖿ⣽⬊㸦& ⣽⬊㸧ࠖ࡜ࡣࠊࣄࢺయ⣽⬊ࢆ㑇ఏᏊᑟධ࣭ࢱࣥࣃࢡ㉁ᑟධ࣭⸆๣ฎ⌮➼࡟ࡼࡾேⅭⓗ࡟ึᮇ໬ࡋ࡚ᚓࡽࢀࡿ⣽⬊ཪࡣᙜヱ⣽⬊ࡢศ⿣࡟ࡼ
ࡾ⏕ࡎࡿ⣽⬊࡛࠶ࡗ࡚ࠊෆ⬇ⴥࠊ୰⬇ⴥཬࡧእ⬇ⴥࡢ⣽⬊࡟ศ໬ࡍࡿᛶ㉁ࢆ᭷ࡋࠊ࠿
ࡘࠊ⮬ᕫ」〇⬟ຊࢆ⥔ᣢࡋ࡚࠸ࡿࡶࡢཪࡣࡑࢀ࡟㢮ࡍࡿ⬟ຊࢆ᭷ࡍࡿࡇ࡜ࡀ᥎ᐃࡉࢀ
ࡿࡶࡢࢆ࠸࠺ࠋ㸰 ࠕࣄࢺேᕤከ⬟ᛶᖿ⣽⬊ᵝ⣽⬊㸦& ᵝ⣽⬊㸧ࠖ࡜ࡣࠊࣄࢺయ⣽⬊ࢆࠊ㑇ఏᏊᑟධ࣭ࢱࣥࣃࢡ㉁ᑟධ࣭⸆๣ฎ⌮➼࡟ࡼࡾேⅭⓗ࡟⬺ศ໬ࡋ࡚ᚓࡽࢀࡿ⣽⬊ཪࡣᙜヱ⣽⬊ࡢศ⿣࡟ࡼࡾ⏕ࡎࡿ⣽⬊࡛࠶ࡗ࡚ࠊᑡ࡞ࡃ࡜ࡶෆ⬇ⴥࠊ୰⬇ⴥཪࡣእ⬇ⴥࡢ୍㒊ࡢ⣽⬊࡟ศ໬ࡍࡿᛶ㉁ࢆ᭷ࡋࠊ⮬ᕫ」〇⬟ࢆ⥔ᣢࡋ࡚࠸ࡿࡶࡢཪࡣࡑࢀ࡟㢮ࡍࡿ⬟ຊࢆ᭷ࡍࡿࡇ࡜ࡀ᥎ᐃࡉࢀࡿࡶࡢࢆᣦࡍࠋ㸱 ࠕ⣽⬊࣭⤌⧊ࡢຍᕤࠖ࡜ࡣࠊ⑌ᝈࡢ἞⒪ࡸ⤌⧊ࡢಟ᚟ཪࡣ෌ᘓࢆ┠ⓗ࡜ࡋ࡚ࠊ⣽⬊࣭⤌⧊ࡢேⅭⓗ࡞ቑṪ࣭ศ໬ࠊ⣽⬊ࡢᰴ໬ࠊ⣽⬊ࡢάᛶ໬➼ࢆ┠ⓗ࡜ࡋࡓ⸆๣ฎ⌮ࠊ⏕≀Ꮫⓗ≉ᛶᨵኚࠊ㠀⣽⬊ᡂศ࡜ࡢ⤌ࡳྜࢃࡏཪࡣ㑇ఏᏊᕤᏛⓗᨵኚ➼ࢆ᪋ࡍࡇ࡜ࢆ
࠸࠺ࠋ⤌⧊ࡢศ㞳ࠊ⤌⧊ࡢ⣽ษࠊ⣽⬊ࡢศ㞳ࠊ≉ᐃ⣽⬊ࡢ༢㞳ࠊᢠ⏕≀㉁࡟ࡼࡿฎ⌮ࠊὙίࠊ࣐࢞ࣥ⥺➼࡟ࡼࡿ⁛⳦ࠊ෭෾ࠊゎ෾➼ࡣຍᕤ࡜ࡳ࡞ࡉ࡞࠸ࠋ
㸲 ࠕ〇㐀ࠖ࡜ࡣࠊຍᕤ࡟ຍ࠼ࠊ⤌⧊ࡢศ㞳ࠊ⤌⧊ࡢ⣽ษࠊ⣽⬊ࡢศ㞳ࠊ≉ᐃ⣽⬊ࡢ༢㞳ࠊᢠ⏕≀㉁࡟ࡼࡿฎ⌮ࠊὙίࠊ࣐࢞ࣥ⥺➼࡟ࡼࡿ⁛⳦ࠊ෭෾ࠊゎ෾➼ࠊᙜヱ⣽⬊࣭⤌⧊ࡢᮏ᮶ࡢᛶ㉁ࢆᨵኚࡋ࡞࠸᧯సࢆྵࡴ⾜Ⅽ࡛ࠊ᭱⤊〇ရ࡛࠶ࡿࣄࢺྠ✀&㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࢆฟⲴࡍࡿࡲ࡛࡟⾜࠺⾜Ⅽࢆ࠸࠺ࠋ㸳 ࠕ⾲⌧ᆺࠖ࡜ࡣࠊ࠶ࡿ୍ᐃࡢ⎔ቃ᮲௳ࡢࡶ࡜࡛ࠊ࠶ࡿ㑇ఏᏊ࡟ࡼࡗ࡚⾲⌧ࡉࢀࡿᙧែᏛⓗཬࡧ⏕⌮Ꮫⓗ࡞ᛶ㉁ࢆ࠸࠺ࠋ㸴 ࠕ ࢱ࢖ࣆࣥࢢࠖ࡜ࡣࠊࣄࢺࡢ୺せ⤌⧊㐺ྜᛶᢠཎᆺ࡛࠶ࡿ ࣄࢺⓑ⾑⌫ᢠཎࡢࢱ࢖ࣉࢆ≉ᐃࡍࡿࡇ࡜ࢆ࠸࠺ࠋ㸵 ࠕࢻࢼ࣮ࠖ࡜ࡣࠊࣄࢺྠ✀& 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢཎᩱ࡜࡞ࡿయ⣽⬊ࢆᥦ౪ࡍࡿࣄࢺࢆ࠸࠺ࠋ㸶 ࠕ㑇ఏᏊᑟධᵓᡂయࠖ࡜ࡣࠊ┠ⓗ㑇ఏᏊࢆᶆⓗ⣽⬊࡟ᑟධࡍࡿࡓࡵࡢ㐠ᦙయࠊ┠ⓗ㑇ఏᏊཬࡧࡑࡢᶵ⬟Ⓨ⌧࡟ᚲせ࡞せ⣲ࢆࢥ࣮ࢻࡍࡿሷᇶ㓄ิ➼࠿ࡽᵓᡂࡉࢀࡿࡶࡢࢆ࠸࠺ࠋ㸷 ࠕࢱࣥࣃࢡ㉁ᑟධయࠖ࡜ࡣࠊ┠ⓗࢱࣥࣃࢡ㉁ࢆᶆⓗ⣽⬊࡟ᑟධࡍࡿࡓࡵࡢ⸆๣ཬࡧ
┠ⓗࢱࣥࣃࢡ㉁➼࠿ࡽᵓᡂࡉࢀࡿࡶࡢࢆ࠸࠺ࠋ

㸫㸫

➨㸰❶ 〇㐀᪉ἲ〇㐀᪉ἲ࡟ࡘ࠸࡚ࠊୗグࡢ஦㡯࡟␃ពࡋࠊᚲせ࡞᝟ሗࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋࡇࢀࡽࡢ
᝟ሗ➼ࡣࠊ᭱⤊〇ရࡢရ㉁ࡸᏳ඲ᛶ➼ࡢ☜ಖ࡟㈨ࡍࡿ࡜࡜ࡶ࡟ࠊရ㉁ࡢᜏᖖᛶࢆ〇㐀᪉ἲ㠃࠿ࡽಖドࡍࡿࡓࡵ࡟㔜せ࡞ࡶࡢ࡛࠶ࡿࠋࡋ࠿ࡋࠊရ㉁࣭Ᏻ඲ᛶ➼ࡢ☜ಖࡸရ㉁ᜏᖖ
ᛶಖドࡣࠊ〇㐀᪉ἲ඲య࡛┦஫⿵᏶ⓗ᪉⟇࡟ࡼࡾ㐩ᡂࡉࢀࠊࡑࡢ᪉⟇ࡀྜ⌮ⓗ࡛ྜ┠ⓗᛶ࡟ྔ࠺ࡇ࡜ࡀ᭱ࡶ⫢せ࡛࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊ᭱⤊〇ရࡸ୰㛫〇ရ࡟࠾ࡅࡿရ㉁ヨ㦂ࡸ⟶⌮࠶ࡿ࠸ࡣ〇㐀㐣⛬࡟࠾ࡅࡿ⟶⌮࡟࠾࠸࡚ࠊရ㉁࣭Ᏻ඲ᛶ➼ࡢ☜ಖࡸရ㉁ᜏᖖᛶಖド࡜࠸࠺┠ⓗࡀ㐩ᡂࡉࢀࡿࡢ࡛࠶ࢀࡤࠊࡑࡢ⛉Ꮫⓗጇᙜᛶࢆ᫂♧ࡋࡓୖ࡛ୗグࡢᥐ⨨ࡸ᝟ሗࡢ୍㒊ࢆ┬␎ࡋ࡚ࡶᕪࡋᨭ࠼࡞࠸ࠋ➨㸯 ཎᮦᩱཬࡧ〇㐀㛵㐃≀㉁
㸯 㸦ᵝ㸧⣽⬊స〇ࡢཎᮦᩱ࡜࡞ࡿࣄࢺయ⣽⬊ ㉳※ཬࡧ⏤᮶ࠊ㑅ᢥ⌮⏤
ࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴࡢᶞ❧࡟౑⏝ࡍࡿయ⣽⬊ࡢ㉳※ཬࡧ⏤᮶࡟ࡘ࠸࡚ㄝ᫂ࡋࠊᙜ
ヱయ⣽⬊ࢆ㑅ᢥࡋࡓ⌮⏤ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
 ཎᮦᩱ࡜࡞ࡿ⣽⬊࣭⤌⧊ࡢ≉ᛶ࡜㐺᱁ᛶձ⏕≀Ꮫⓗᵓ㐀࣭ᶵ⬟ࡢ≉ᚩ࡜㑅ᢥ⌮⏤ཎᮦᩱ࡜ࡋ࡚⏝࠸ࡽࢀࡿ⣽⬊࣭⤌⧊࡟ࡘ࠸࡚ࠊࡑࡢ⏕≀Ꮫⓗᵓ㐀࣭ᶵ⬟ࡢ≉ᚩࢆࠊ౛࠼ࡤࠊᙧែᏛⓗ≉ᚩࠊቑṪ≉ᛶࠊ⏕໬Ꮫⓗᣦᶆࠊච␿Ꮫⓗᣦᶆࠊ≉ᚩⓗ⏘⏕≀㉁ࠊ
 ࢱ࢖ࣆࣥࢢࠊࡑࡢ௚㐺ษ࡞㑇ఏᆺཪࡣ⾲⌧ᆺࡢᣦᶆ࠿ࡽ㐺ᐅ㑅ᢥࡋ࡚♧ࡋࠊᙜヱయ⣽⬊ࢆཎᮦᩱ࡜ࡋ࡚㑅ᢥࡋࡓ⌮⏤ࢆㄝ᫂ࡍࡿࡇ࡜ࠋ
ࡇࢀࡽࡢ᳨ウ⤖ᯝ࠿ࡽཎᮦᩱ࡜࡞ࡿయ⣽⬊ࢆ᪂ࡓ࡟ㄪ〇ࡍࡿ㝿࡟㑅ᢥࡍ࡭ࡁ㔜せ⣽⬊≉ᛶᣦᶆࢆ᫂ࡽ࠿࡟ࡋ࡚࠾ࡃࡇ࡜ࠋ᳨ウ࡟㝿ࡋ࡚ࡣࠊ᳨యࡢ㔞ⓗไ㝈ࡸᢏ⾡ⓗ㝈⏺ࡶ࠶ࡾࠊྍ⬟࡞⠊ᅖ࡛⪃៖ࡍࢀࡤⰋ࠸ࠋ
ղࢻࢼ࣮ࡢ㑅ᢥᇶ‽ࠊ㐺᱁ᛶࢻࢼ࣮ࡢ㑅ᢥࡀ೔⌮ⓗ࡟㐺ษ࡟⾜ࢃࢀࠊ࠿ࡘ㐺ษ࡞ᡭ⥆ࡁ࡛⾜ࢃࢀࡓࡇ࡜ࢆ♧ࡍࡇ࡜ࠋࡲࡓࠊᖺ㱋ࠊᛶูࠊẸ᪘Ꮫⓗ≉ᚩࠊ㑇ఏⓗ≉ᚩࠊ⑓Ṕࠊ೺ᗣ≧ែࠊ᥇ྲྀ⣽⬊࣭⤌⧊ࢆ௓ࡋ࡚ឤᰁࡍࡿྍ⬟ᛶࡀ࠶ࡿྛ✀ឤᰁ⑕࡟㛵ࡍࡿ᳨ᰝ㡯┠ࠊච␿㐺ྜᛶ➼ࢆ⪃៖ࡋ࡚ࠊ㑅ᢥᇶ‽ࠊ㐺᱁ᛶᇶ‽ࢆᐃࡵࠊࡑࡢጇᙜᛶࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋࢻࢼ
࣮ࡢࢤࣀ࣒࣭㑇ఏᏊゎᯒࢆ⾜࠺ሙྜࡣࠊࠕࣄࢺࢤࣀ࣒࣭㑇ఏᏊゎᯒ◊✲࡟㛵ࡍࡿ೔⌮ᣦ㔪ࠖ㸦ᖹᡂ  ᖺᩥ㒊⛉Ꮫ┬࣭ཌ⏕ປാ┬࣭⤒῭⏘ᴗ┬࿌♧➨  ྕ㸧࡟ᚑ࠺ࡇ࡜ࠋឤᰁ⑕࡟㛵㐃ࡋ࡚ࡣࠊ≉࡟  ᆺ⫢⅖"ࠊ ᆺ⫢⅖"ࠊࣄࢺච␿୙඲࢘࢖ࣝ
ࢫ"ឤᰁ⑕ࠊᡂே ! ⣽⬊ⓑ⾑⑓!"ࠊࣃࣝ࣎࢘࢖ࣝࢫ  ឤᰁ⑕࡟ࡘ࠸࡚ࡣࠊ
ၥデཬࡧ᳨ᰝ⾑ΎᏛⓗヨ㦂ࡸ᰾㓟ቑᖜἲ➼࡟ࡼࡾྰᐃࡍࡿࡇ࡜ࠋࡲࡓࠊࢧ࢖ࢺ࣓
࢞ࣟ࢘࢖ࣝࢫឤᰁࠊ ࢘࢖ࣝࢫឤᰁཬࡧ࢚࢘ࢫࢺࢼ࢖ࣝ࢘࢖ࣝࢫឤᰁ࡟ࡘ࠸࡚ࡣᚲせ࡟ᛂࡌ᳨࡚ᰝ࡟ࡼࡾྰᐃࡍࡿࡇ࡜ࠋ
ࡇࡢ௚ࠊḟ࡟ᥖࡆࡿࡶࡢ࡟ࡘ࠸࡚ࡣ᪤ Ṕࡢ⫈ྲྀࠊၥデ➼ࢆ⾜࠺࡜࡜ࡶ࡟ࠊ㍺⾑ࠊ⛣᳜་⒪ࢆཷࡅࡓ⤒㦂ࡢ᭷↓➼࠿ࡽࢻࢼ࣮࡜ࡋ࡚ࡢ㐺᱁ᛶࢆุ᩿ࡍࡿࡇ࡜ࠋ
࣭ᱵẘࢺ࣏ࣞࢿ࣮࣐ࠊࢡ࣑ࣛࢪ࢔ࠊ᾿⳦ࠊ⤖᰾⳦➼ࡢ⣽⳦࡟ࡼࡿឤᰁ⑕ 
㸫㸫

࣭ᩋ⾑⑕ཬࡧࡑࡢ␲࠸࣭ᝏᛶ⭘⒆
࣭㔜⠜࡞௦ㅰཬࡧෆศἪ⑌ᝈ
࣭⭺ཎ⑓ཬࡧ⾑ᾮ⑌ᝈ࣭⫢⑌ᝈ࣭ఏ㐩ᛶᾏ⥥≧⬻⑕ཬࡧࡑࡢ␲࠸୪ࡧ࡟ࡑࡢ௚ࡢㄆ▱⑕࣭≉ᐃࡢ㑇ఏᛶ⑌ᝈࡸᐙ᪘Ṕ࡞࠾ࠊ≉ᐃࡢ㑇ఏⓗ≉ᚩࡸྛ✀ឤᰁ⑕࡟㛵ࡍࡿㄪᰝ➼࡛ & 㸦ᵝ㸧⣽⬊࠿ࡽศ໬ࡀ㐍ࢇࡔ⣽⬊ࡢẁ㝵㸦୰㛫〇ရࡸࢭ࣭ࣝࣂࣥࢡ㸧࡛⾜࠺ࡇ࡜ࡀྍ⬟࡛ࠊ࠿ࡘ⛉Ꮫⓗྜ⌮ᛶ࠿ࡽࡳ࡚ࡼࡾ㐺ษ࡞㡯┠࡟ࡘ࠸࡚ࡣࠊࡑࡢጇᙜᛶࢆ᫂♧ࡋࡓୖ࡛ࠊศ໬⣽⬊ࡢẁ㝵࡛ࡢ᳨ウ࡟ጤࡡ࡚ࡶࡼ࠸ࠋ
 ࢻࢼ࣮࡟㛵ࡍࡿグ㘓ཎᮦᩱ࡜࡞ࡿయ⣽⬊࡟ࡘ࠸࡚ࠊᏳ඲ᛶࢆ☜ಖࡍࡿࡓࡵ࡟ᚲせ࡞᝟ሗࡀ☜ㄆ࡛ࡁࡿࡼ
࠺ࠊࢻࢼ࣮࡟㛵ࡍࡿグ㘓ࡀᩚഛࠊಖ⟶ࡉࢀ࡚࠸ࡿࡇ࡜ࠋࡲࡓࠊࡑࡢලయⓗ᪉⟇ࢆ♧ࡍࡇ࡜ࠋ࡞࠾ࠊヨ㦂ⓗ᳨యࡢࢻࢼ࣮ཬࡧᝈ⪅ࡢࡑࢀࡒࢀ࡟ࡘ࠸࡚ࠊࡑࢀࡒࢀࡢ⣽⬊ࡢ౑⏝┠ⓗ࡟ᛂࡌࡓ᝟ሗࡢᩚഛཬࡧಖ⟶᪉⟇࡛ࡼ࠸ࠋ
 ⣽⬊࣭⤌⧊ࡢ᥇ྲྀ࣭ಖᏑ࣭㐠ᦙձ᥇ྲྀ⪅ཬࡧ᥇ྲྀ་⒪ᶵ㛵➼ࡢ㐺᱁ᛶ⣽⬊࣭⤌⧊ࡢ᥇ྲྀ⪅ཬࡧ᥇ྲྀ་⒪ᶵ㛵➼࡟ồࡵࡿ࡭ࡁᢏ⾡ⓗせ௳࡟ࡘ࠸࡚ࠊ᫂ࡽ
࠿࡟ࡍࡿࡇ࡜ࠋ
ղ᥇ྲྀ㒊఩ཬࡧ᥇ྲྀ᪉ἲࡢጇᙜᛶ
⣽⬊࣭⤌⧊ࡢ᥇ྲྀ㒊఩ࡢ㑅ᐃᇶ‽ཬࡧ᥇ྲྀ᪉ἲࢆ♧ࡋࠊࡇࢀࡽࡀ⛉Ꮫⓗཬࡧ೔⌮ⓗ࡟㐺ษ࡟㑅ᢥࡉࢀࡓࡶࡢ࡛࠶ࡿࡇ࡜ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ⣽⬊࣭⤌⧊ࡢ᥇ྲྀ᪉ἲ
࡟ࡘ࠸࡚ࡣࠊ⏝࠸ࡽࢀࡿჾලཬࡧ⸆๣ࠊᚤ⏕≀ởᰁ㜵Ṇࠊྲྀࡾ㐪࠼ࡸࢡࣟࢫࢥࣥࢱ
࣑ࢿ࣮ࢩࣙࣥ㜵Ṇࡢࡓࡵࡢ᪉⟇➼ࢆලయⓗ࡟♧ࡍࡇ࡜ࠋ
ճࢻࢼ࣮࡟ᑐࡍࡿㄝ᫂ཬࡧྠព
⣽⬊࣭⤌⧊ࡢࢻࢼ࣮࡟ᑐࡍࡿㄝ᫂ཬࡧྠពࡢෆᐜࢆࠊ⮫ᗋᛂ⏝ࡶྵࡵ࡚つᐃࡍࡿࡇ࡜ࠋմࢻࢼ࣮ࡢಶே᝟ሗࡢಖㆤ
ࢻࢼ࣮ࡢಶே᝟ሗࡢಖㆤ᪉⟇࡟ࡘ࠸࡚ලయⓗ࡟つᐃࡍࡿࡇ࡜ࠋ
յࢻࢼ࣮ࡢᏳ඲ᛶ☜ಖࡢࡓࡵࡢヨ㦂᳨ᰝ⣽⬊࣭⤌⧊᥇ྲྀ᫬࡟ࢻࢼ࣮ࡢᏳ඲ᛶ☜ಖࡢࡓࡵ࡟᥇ྲྀ㒊఩ࡢ≧ែࡢ☜ㄆ࡞࡝ヨ㦂᳨ᰝࢆ⾜ࢃ࡞ࡅࢀࡤ࡞ࡽ࡞࠸ሙྜ࡟ࡣࠊࡑࡢෆᐜࠊ᳨ᰝ⤖ᯝ➼࡟ၥ㢟ࡀ࠶ࡗࡓሙྜ
ࡢᑐฎἲ࡟ࡘ࠸࡚ලయⓗ࡟つᐃࡍࡿࡇ࡜ࠋ
նಖᏑ᪉ἲཬࡧྲྀࡾ㐪࠼㜵Ṇ⟇᥇ྲྀࡋࡓయ⣽⬊ࢆ୍ᐃᮇ㛫ಖᏑࡍࡿᚲせࡀ࠶ࡿሙྜ࡟ࡣࠊಖᏑ᮲௳ࡸಖᏑᮇ㛫ཬࡧࡑࡢタᐃࡢጇᙜᛶ࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋࡲࡓࠊྲྀࡾ㐪࠼ࢆ㑊ࡅࡿࡓࡵࡢᡭ
ẁࡸᡭ㡰➼࡟ࡘ࠸࡚ලయⓗ࡟ㄝ᫂ࡍࡿࡇ࡜ࠋ 
㸫㸫

շ㐠ᦙ᪉ἲ
᥇ྲྀࡋࡓ⣽⬊࣭⤌⧊ࡸ & 㸦ᵝ㸧⣽⬊స〇ཎᩱ࡜࡞ࡿయ⣽⬊ࢆ㐠ᦙࡍࡿᚲせࡀ࠶ࡿሙྜ࡟ࡣࠊ㐠ᦙᐜჾࠊ㐠ᦙᡭ㡰 ᗘ⟶⌮➼ࢆྵࡴࠋࢆᐃࡵࠊࡑࡢጇᙜᛶ࡟ࡘ࠸
࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
ոグ㘓ࡢసᡂཬࡧಖ⟶᪉ἲձ㹼շ࡟㛵ࡍࡿ஦㡯࡟ࡘ࠸࡚ࠊᐇ᪋ࡢグ㘓ࢆᩥ᭩࡛సᡂࡋࠊ㐺ษ࡟ಖ⟶ࡍࡿ᪉ἲ࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ㸰 ┠ⓗ࡜ࡍࡿ⣽⬊࣭⤌⧊௨እࡢཎᮦᩱཬࡧ〇㐀㛵㐃≀㉁୪ࡧ࡟〇㐀㛵㐃஦㡯┠ⓗ࡜ࡍࡿ⣽⬊࣭⤌⧊௨እࡢཎᮦᩱཬࡧ〇㐀㛵㐃≀㉁୪ࡧ࡟〇㐀㛵㐃஦㡯ࢆ᫂ࡽ࠿࡟ࡋࠊࡑࡢ㐺᱁ᛶࢆ♧ࡍ࡜࡜ࡶ࡟ࠊᚲせ࡟ᛂࡌ࡚つ᱁ࢆタᐃࡋࠊ㐺ษ࡞ရ㉁⟶⌮ࢆ⾜࠺ࡇ࡜ࡀᚲせ࡛࠶ࡿࠋ⏕≀⏤᮶〇ရཪࡣ≉ᐃ⏕≀⏤᮶〇ရࢆཎᮦᩱ࡜ࡋ࡚౑⏝ࡍࡿሙྜࡣࠊࡑࡢ౑⏝㔞ࢆᚲせ᭱ᑠ㝈࡜ࡋࠊࠕ⏕≀⏤᮶ཎᩱᇶ‽ࠖᖹᡂ  ᖺཌ⏕ປാ┬࿌♧➨  ྕࢆࡣࡌ
ࡵ࡜ࡍࡿ㛵㐃ἲ௧ཬࡧ㏻▱ࢆ㑂Ᏺࡍࡿࡇ࡜ࠋ≉࡟ࠊ࢘࢖ࣝࢫ୙ά໬ཬࡧ㝖ཤ࡟㛵ࡍࡿ᝟ሗࢆ༑ศ࡟ホ౯ࡍࡿᚲせࡀ࠶ࡿ࡯࠿ࠊ㐳ཬㄪᰝ➼ࢆ☜ಖࡍࡿ᪉⟇࡟ࡘ࠸࡚ࡶ᫂ࡽ࠿
࡟ࡍࡿࡇ࡜ࠋ
࡞࠾ࠊࡇࡢ㡯࡟グ㍕ࡉࢀࡓᢏ⾡せ௳ࡣࠊ& 㸦ᵝ㸧⣽⬊స〇ࡢཎᮦᩱ࡜࡞ࡿࣄࢺయ
⣽⬊࠿ࡽ & 㸦ᵝ㸧⣽⬊࡬ࡢึᮇ໬ࡸ⬺ศ໬ཬࡧ & 㸦ᵝ㸧⣽⬊࠿ࡽ᭱⤊〇ရ࡟⮳ࡿศ໬ㄏᑟ㐣⛬࡟࠾࠸࡚ヱᙜࡍࡿሙྜ࡟␃ពࡉࢀࡿ࡭ࡁ஦㡯࡛࠶ࡿࠋ
 ⣽⬊ࡢᇵ㣴ࢆ⾜࠺ሙྜձᇵᆅࠊῧຍᡂศ⾑Ύࠊᡂ㛗ᅉᏊཬࡧᢠ⏕≀㉁➼ཬࡧ⣽⬊ࡢฎ⌮࡟⏝࠸ࡿヨ⸆➼ࡢࡍ࡭࡚ࡢᡂศ➼࡟ࡘ࠸࡚ࡑࡢ㐺᱁ᛶࢆ᫂ࡽ࠿࡟ࡋࠊᚲせ࡟ᛂࡌ࡚つ᱁ࢆタᐃࡍࡿࡇ࡜ࠋྛᡂศ➼ࡢ㐺᱁ᛶࡢุᐃཬࡧつ᱁ࡢタᐃ࡟ᙜࡓࡗ࡚ࡣࠊ᭱⤊〇ရࡢ㐺⏝⤒㊰➼ࢆ⪃៖ࡍࡿࡇ࡜ࠋ
ղᇵᆅᡂศ࡟ࡘ࠸࡚ࡣࠊ௨ୗࡢⅬ࡟␃ពࡍࡿࡇ࡜ࠋ࢔ ᇵᆅ࡟౑⏝ࡍࡿᡂศཬࡧỈࡣࠊྍ⬟࡞⠊ᅖ࡛་⸆ရཪࡣ་⸆ရཎᩱ࡟┦ᙜࡍࡿᇶ‽࡛ရ㉁⟶⌮ࡉࢀ࡚࠸ࡿ⏕≀Ꮫⓗ⣧ᗘࡢ㧗࠸ရ㉁ࡢࡶࡢࢆ౑⏝ࡍࡿࡇ࡜ࠋ࢖ ᇵᆅ࡟౑⏝ࡍࡿᡂศࡣ୺ᡂศࡢࡳ࡛࡞ࡃ౑⏝ࡍࡿࡍ࡭࡚ࡢᡂศ࡟ࡘ࠸࡚᫂ࡽ
࠿࡟ࡋࠊ㑅ᢥ⌮⏤ཬࡧᚲせ࡟ᛂࡌ࡚ရ㉁⟶⌮ἲ➼ࢆ᫂☜࡟ࡍࡿࡇ࡜ࠋࡓࡔࡋࠊᇵ
ᆅࡢᵓᡂᡂศࡀ࿘▱ࡢࡶࡢ࡛ࠊᕷ㈍ရ➼ࡀ୍⯡ⓗ࡟౑⏝ࡉࢀ࡚࠸ࡿ ࠊࠊ
ࠊ ࡢࡼ࠺࡞ᇵᆅࡣ  ࡘࡢࡶࡢ࡜⪃࠼࡚ࡼ࠸ࠋ࢘ ࡍ࡭࡚ࡢᡂศࢆྵ᭷ࡋࡓᇵᆅࡢ᭱⤊ရ࡟ࡘ࠸࡚ࡣࠊ↓⳦ᛶཬࡧ┠ⓗ࡜ࡋࡓᇵ㣴࡟㐺ࡋ࡚࠸ࡿࡇ࡜ࢆุᐃࡍࡿࡓࡵࡢᛶ⬟ヨ㦂ࢆᐇ᪋ࡍࡿᚲせࡀ࠶ࡿࠋࡑࡢ௚ࠊᕤ
⛬⟶⌮ୖᚲせ࡜ᛮࢃࢀࡿヨ㦂㡯┠ࢆつ᱁࡜ࡋ࡚タᐃࡋࠊ㐺ษ࡞ရ㉁⟶⌮ࢆ⾜࠺ᚲせࡀ࠶ࡿࠋ
ճ␗✀⾑Ύཬࡧ␗✀ࡶࡋࡃࡣྠ✀ࡢ⾑Ύ࡟⏤᮶ࡍࡿᡂศ࡟ࡘ࠸࡚ࡣࠊ⣽⬊άᛶ໬ཪࡣ
ቑṪ➼ࡢຍᕤ࡟ᚲ㡲࡛࡞ࡅࢀࡤ౑⏝ࡋ࡞࠸ࡇ࡜ࠋ≉࡟⧞ࡾ㏉ࡋ࡚౑⏝ࡍࡿྍ⬟ᛶࡢ࠶ࡿ〇ရ࡛ࡣྍ⬟࡞㝈ࡾ౑⏝ࢆ㑊ࡅࡿࡼ࠺᳨ウࡍࡿࡇ࡜ࠋ⾑Ύ➼ࡢ౑⏝ࡀ㑊ࡅࡽࢀ࡞࠸ሙྜ࡟ࡣࠊ௨ୗࡢⅬࢆ⪃៖ࡋࠊ⾑Ύ➼࠿ࡽࡢ⣽⳦ࠊ┿⳦ࠊ࢘࢖ࣝࢫཬࡧ␗ᖖࣉ 
㸫㸫

ࣜ࢜ࣥ➼ࡢΰධ࣭ఏ᧛ࢆ㜵Ṇࡍࡿ࡜࡜ࡶ࡟ࠊ᭱⤊〇ရ࠿ࡽྍ⬟࡞㝈ࡾ㝖ཤࡍࡿࡼ࠺
ฎ⌮᪉ἲ➼ࢆ᳨ウࡍࡿࡇ࡜ࠋ࢔ ⾑Ύ➼ࡢ⏤᮶ࢆ᫂☜࡟ࡍࡿࡇ࡜ࠋ࢖ ∵ᾏ⥥≧⬻⑕Ⓨ⏕ᆅᇦ࠿ࡽࡢ⾑Ύࢆᴟຊ㑊ࡅࡿ➼ឤᰁ⑕ࣜࢫࢡࡢపῶ࡟ດࡵࡿࡇ࡜ࠋ࢘ ⏤᮶ື≀✀࡟≉␗ⓗ࡞࢘࢖ࣝࢫࡸ࣐࢖ࢥࣉࣛࢬ࣐࡟㛵ࡍࡿ㐺ษ࡞ྰᐃヨ㦂ࢆ⾜࠸ࠊ࢘࢖ࣝࢫ➼࡟ởᰁࡉࢀ࡚࠸࡞࠸ࡇ࡜ࢆ☜ㄆࡋࡓୖ࡛౑⏝ࡍࡿࡇ࡜ࠋ࢚ ⣽⬊ࡢάᛶ໬ࠊቑṪ࡟ᙳ㡪ࢆ୚࠼࡞࠸⠊ᅖ࡛⣽⳦ࠊ┿⳦ཬࡧ࢘࢖ࣝࢫ➼࡟ᑐࡍࡿ㐺ษ࡞୙ά໬ฎ⌮ཬࡧ㝖ཤฎ⌮ࢆ⾜࠺ࠋ౛࠼ࡤࠊ₯ᅾⓗ࡞࢘࢖ࣝࢫΰධࡢ༴㝤ᛶࢆ㑊ࡅࡿࡓࡵ࡟ࠊᚲせ࡟ᛂࡌ࡚ຍ⇕ฎ⌮ࠊࣇ࢕ࣝࢱ࣮ฎ⌮ࠊᨺᑕ⥺ฎ⌮ཪࡣ⣸እ⥺ฎ⌮➼ࢆ⤌ࡳྜࢃࡏ࡚⾜࠺ࡇ࡜ࠋ࢜ ᇵ㣴⣽⬊࡛ࡢ࢘࢖ࣝࢫឤᰁࡢࣔࢽࢱ࣮ࠊᝈ⪅࡛ࣞ࣋ࣝࡢ࢘࢖ࣝࢫᛶ⑌ᝈࡢⓎ⑕࡟ᑐࡍࡿࣔࢽࢱ࣮ཬࡧ␗✀⾑Ύᡂศ࡟ᑐࡍࡿᢠయ⏘⏕➼ࡢㄪᰝࡢࡓࡵ࡟ࠊ౑⏝ࡋࡓ⾑Ύࡢ୍㒊ࢆಖ⟶ࡍࡿࡇ࡜ࠋ
մࣇ࢕࣮ࢲ࣮⣽⬊ࢆ౑⏝ࡍࡿሙྜ࡟ࡣࠊᖹᡂ  ᖺ ᭶  ᪥௜ࡅ་⸆ᑂ➨  ྕ㏻▱ཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ㛗㏻▱ࠕ⏕≀⸆ရ㸦ࣂ࢖࢜ࢸࢡࣀࣟࢪ࣮ᛂ⏝་⸆ရ㸭⏕≀㉳※⏤᮶་⸆ရ㸧〇㐀⏝⣽⬊ᇶ๣ࡢ⏤᮶ࠊㄪ〇ཬࡧ≉ᛶゎᯒࠖࠊᖹᡂ ᖺ ᭶  ᪥௜ࡅ་ᨻ◊Ⓨ➨   ྕཌ⏕ປാ┬་ᨻᒁ◊✲㛤Ⓨ᣺⯆ㄢ㛗㏻▱ࠕ␗✀⛣᳜ࡢᐇ᪋࡟క࠺බ⾗⾨⏕ୖࡢឤᰁ⑕ၥ㢟࡟㛵ࡍࡿᣦ㔪ࠖཬࡧᖹᡂ  ᖺ ᭶ ᪥௜་ᨻ◊Ⓨ➨   ྕཌ⏕ປാ┬་ᨻᒁ◊✲㛤Ⓨ᣺⯆ㄢ㛗㏻▱ࠕࠕ␗✀⛣᳜ࡢᐇ᪋࡟క࠺බ⾗⾨⏕ୖࡢឤᰁ⑕ၥ㢟࡟㛵ࡍࡿᣦ㔪ࠖ࡟ᇶ࡙ࡃ !  ᰴཬࡧ ! ᰴࢆࣇ࢕࣮ࢲ࣮⣽⬊࡜ࡋ࡚฼⏝ࡍࡿୖ⓶⣔ࡢ෌⏕་⒪࡬ࡢᣦ㔪ࠖࢆཧ⪃࡟ࡋ࡚ရ㉁ホ౯ࢆ⾜࠸ࠊࣇ࢕࣮ࢲ࣮⣽⬊࠿ࡽࡢ⣽⳦ࠊ┿⳦ࠊ࢘࢖ࣝࢫࠊ␗ᖖࣉࣜ࢜ࣥ➼ࡢΰධ࣭ఏ᧛ࢆ㜵Ṇࡍࡿ⟇ࢆㅮࡌࡿ࡜࡜ࡶ࡟ࠊ౑⏝᫬ࡢศ⿣⬟୙ά໬᪉ἲཬࡧ⣽⬊ᐦᗘ➼ࡢ᮲௳࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋࡓࡔࡋࠊ౛࠼ࡤ᪤࡟⮫ᗋ౑⏝ࡉࢀ࡚࠸ࡿࣄࢺ⣽⬊࣭⤌⧊〇ရࡢ〇㐀࡟౑⏝ࡉࢀࠊࡑࡢ≉ᛶࡸᚤ⏕≀ᏛⓗᏳ඲ᛶ➼࡟ࡘ࠸࡚ホ౯ࡀᐃࡲࡗ࡚࠸ࡿࣇ࢕࣮ࢲ࣮⣽⬊࡜ྠ୍ࡢ⣽⬊ࢆ฼⏝ࡍࡿሙྜ࡟ࡣࠊࡑࡢጇᙜᛶࢆ♧ࡍࡇ࡜࡟ࡼࡗ࡚࢘࢖ࣝࢫྰᐃヨ㦂➼ࠊヨ㦂ࡢ୍㒊ࢆ┬␎ࡍࡿࡇ࡜ࡀ࡛ࡁࡿྍ⬟ᛶࡀ࠶ࡿࠋյᢠ⏕≀㉁ࡢ౑⏝ࡣᴟຊ㑊ࡅࡿ࡭ࡁ࡛࠶ࡿࠋࡓࡔࡋ〇㐀ึᮇࡢᕤ⛬࡟࠾࠸࡚ᢠ⏕≀㉁ࡢ౑⏝ࡀ୙ྍḞ࡜⪃࠼ࡽࢀࡿሙྜ࡟ࡣࠊࡑࡢᚋࡢᕤ⛬࡛ྍ⬟࡞㝈ࡾ₞ῶࢆᅗࡿ࡯
࠿ࠊࡑࡢ⛉Ꮫⓗ⌮⏤ࠊ᭱⤊〇ရ࡛ࡢ᥎ᐃṧᏑ㔞ࠊᝈ⪅࡟ཬࡰࡍᙳ㡪࡞࡝ࡢ㠃࠿ࡽጇᙜᛶࢆㄝ᫂ࡍࡿࡇ࡜ࠋ࡞࠾ࠊᢠ⏕≀㉁ࢆ౑⏝ࡍࡿሙྜ࡛ࡶ༑ศ࡟㝖ཤࡉࢀࡿࡇ࡜ࡀ
❧ドࡉࢀࡿሙྜ࡟ࡣࠊࡑࡢ౑⏝ࢆጉࡆࡿࡶࡢ࡛ࡣ࡞࠸ࠋ୍᪉ࠊཎ๎࡜ࡋ࡚ࠊ⏝࠸ࡿᢠ⏕≀㉁࡟㐣ᩄ⑕ࡢ᪤ Ṕࡢ࠶ࡿᝈ⪅ࡢሙྜ࡟ࡣࠊᮏ἞⒪ࢆ㐺ᛂࡍ࡭ࡁ࡛ࡣ࡞࠸ࠋ
ࡸࡴࢆᚓࡎ㐺⏝ࡍࡿ㝿࡟ࡣ༑ศ࡞ὀពࢆᡶ࠺࡜ྠ᫬࡟ࠊᝈ⪅࠿ࡽ࢖ࣥࣇ࢛࣮࣒ࢻ࣭
ࢥࣥࢭࣥࢺࢆᚓࡿᚲせࡀ࠶ࡿࠋ
նᡂ㛗ᅉᏊࢆ⏝࠸ࡿሙྜ࡟ࡣࠊ⣽⬊ᇵ㣴≉ᛶࡢ෌⌧ᛶࢆಖドࡍࡿࡓࡵ࡟ࠊ౛࠼ࡤ⣧ᗘཬࡧຊ౯࡟㛵ࡍࡿつ᱁ࢆタᐃࡍࡿ➼㐺ษ࡞ရ㉁⟶⌮ἲࢆ♧ࡍࡇ࡜ࠋ
շ᭱⤊〇ရ࡟ྵ᭷ࡍࡿྍ⬟ᛶࡢ࠶ࡿᇵᆅᡂศࡸ᧯సࡢࡓࡵ࡟⏝࠸ࡽࢀࡓࡑࡢ௚ࡢᡂ 
㸫㸫

ศ➼࡟ࡘ࠸࡚ࡣࠊ⏕య࡟ᝏᙳ㡪ࢆཬࡰࡉ࡞࠸ࡶࡢࢆ㑅ᢥࡍࡿࡇ࡜ࠋ
ոࣇ࢕࣮ࢲ࣮⣽⬊࡜ࡋ࡚␗✀ື≀⏤᮶ࡢ⣽⬊ࢆ⏝࠸ࡿሙྜ࡟ࡣࠊ␗✀ື≀⏤᮶ࡢឤᰁ⑕ࡢࣜࢫࢡࡢほⅬ࠿ࡽᏳ඲ᛶࢆ☜ಖࡍࡿࡇ࡜ࠋ
 㠀⣽⬊ᡂศ࡜⤌ࡳྜࢃࡏࡿሙྜ
ձ⣽⬊௨እࡢཎᮦᩱࡢရ㉁ཬࡧᏳ඲ᛶ࡟ࡘ࠸࡚
⣽⬊࡜࡜ࡶ࡟᭱⤊〇ရࡢ୍㒊ࢆᵓᡂࡍࡿ㠀⣽⬊ࡢཎᮦᩱ࣐ࢺࣜࢵࢡࢫࠊ་⒪ᮦ
ᩱࠊࢫ࢟ࣕࣇ࢛࣮ࣝࢻࠊᨭᣢ⭷ࠊࣇ࢓࢖ࣂ࣮ཬࡧࣅ࣮ࢬ➼ࡀ࠶ࡿሙྜ࡟ࡣࠊࡑࡢ
ရ㉁ཬࡧᏳ඲ᛶ࡟㛵ࡍࡿ▱ぢ࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
ᙜヱཎᮦᩱࡢ✀㢮࡜≉ᛶࠊ᭱⤊〇ရ࡟࠾ࡅࡿᙧែ࣭ᶵ⬟ཬࡧ᝿ᐃࡉࢀࡿ⮫ᗋ㐺ᛂࡢほⅬ࠿ࡽぢࡓရ㉁ࠊᏳ඲ᛶཬࡧ᭷ຠᛶホ౯࡜ࡢ㛵㐃ࢆ຺᱌ࡋ࡚ࠊ㐺ษ࡞᝟ሗࢆᥦ
౪ࡍࡿࡇ࡜ࠋ⏕య྾཰ᛶᮦᩱࢆ⏝࠸ࡿሙྜ࡟ࡣࠊศゎ⏕ᡂ≀࡟㛵ࡋ࡚ᚲせ࡞ヨ㦂ࢆᐇ᪋ࡍࡿࡇ࡜ࠋ
࡞࠾ࠊᚲせ࡞ヨ㦂➼࡟ࡘ࠸࡚ࡣࠊᖹᡂ  ᖺ  ᭶  ᪥௜ࡅ་⸆ᑂⓎ➨  ྕཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ㛗㏻▱ࠕ་⒪⏝ලࡢ〇㐀㍺ධᢎㄆ⏦ㄳ࡟ᚲせ࡞⏕≀Ꮫⓗヨ㦂ࡢᇶᮏⓗ⪃࠼᪉࡟ࡘ࠸࡚ࠖ➼ࢆཧ↷ࡋࠊヨ㦂⤖ᯝཬࡧᙜヱཎᮦᩱࢆ౑⏝ࡍࡿࡇ࡜ࡢጇᙜᛶࢆ♧ࡍࡇ࡜ࠋᩥ⊩࠿ࡽࡢ▱ぢࠊ᝟ሗࢆྜ⌮ⓗ࡟ά⏝ࡍࡿࡇ࡜ࠋ
ղ┠ⓗ࡜ࡍࡿ⣽⬊࡜ࡢ┦஫స⏝࡟ࡘ࠸࡚
᭱⤊〇ရ୰ཪࡣ୰㛫〇ရ୰ࡢ⣽⬊࡜ࡢ┦஫స⏝࡟㛵ࡋࠊ௨ୗࡢ஦㡯࡟ࡘ࠸࡚ࠊ
☜ㄆ᪉ἲཬࡧ☜ㄆ⤖ᯝࢆ♧ࡍࡇ࡜ࠋ࢔ 㠀⣽⬊ᡂศࡀࠊ᝿ᐃࡉࢀࡿ⮫ᗋ㐺ᛂ࡟ᚲせ࡞᭱⤊〇ရ୰ཪࡣ୰㛫〇ရ୰ࡢ⣽⬊ࡢᶵ⬟ࠊ⏕⫱⬟ຊࠊάᛶཬࡧᏳᐃᛶ࡟ᝏᙳ㡪ࢆ୚࠼࡞࠸ࡇ࡜ࠋ࢖ 㠀⣽⬊ᡂศ࡜ࡢ┦஫స⏝࡟ࡼࡗ࡚㉳ࡇࡾᚓࡿࠊ᭱⤊〇ရ୰ཪࡣ୰㛫〇ရ୰ࡢ⣽⬊ࡢኚ␗ࠊᙧ㉁㌿᥮ཬࡧ⬺ศ໬➼ࢆ⪃៖ࡋࠊࡑࡢᙳ㡪ࢆྍ⬟࡞⠊ᅖ࡛ホ౯ࡍࡿࡇ࡜ࠋ࢘ ᝿ᐃࡉࢀࡿ⮫ᗋ㐺ᛂ࡟࠾࠸࡚ᮇᚅࡉࢀࡿ㠀⣽⬊ᡂศࡢᛶ㉁ࡀࠊ᭱⤊〇ရ୰ཪࡣ୰㛫〇ရ୰ࡢ⣽⬊࡜ࡢ┦஫స⏝࡟ࡼࡗ࡚ᦆ࡞ࢃࢀ࡞࠸ࡇ࡜ࠋ
ճ⣽⬊࡜㐺⏝㒊఩ࢆ㝸㞳ࡍࡿ┠ⓗ࡛㠀⣽⬊ᡂศࢆ౑⏝ࡍࡿሙྜ
㠀⣽⬊ᡂศࢆ⣽⬊࡜㐺⏝㒊఩ࢆ㝸㞳ࡍࡿ┠ⓗ࡛౑⏝ࡍࡿሙྜࠊୗグࡢ㡯┠ࢆཧ⪃࡟ຠᯝࠊᏳ඲ᛶࢆ☜ㄆࡍࡿࡇ࡜ࠋ࢔ ච␿㝸㞳ࡀ┠ⓗࡢሙྜࠊࡑࡢ⛬ᗘ࢖ ᭱⤊〇ရ୰ࡢ⣽⬊⏤᮶ࡢ┠ⓗ⏕⌮άᛶ≀㉁ࡢ⭷㏱㐣࢟ࢿࢸ࢕ࢡࢫ࡜⸆⌮ຠᯝ࢘ ᰤ㣴ᡂศཬࡧ᤼ἥ≀ࡢᣑᩓ࢚ 㠀⣽⬊ᡂศࡀ㐺⏝㒊఩࿘㎶࡟ཬࡰࡍᙳ㡪࢜ ┠ⓗ⣽⬊⏤᮶ࡢ┠ⓗ⏕⌮άᛶ≀㉁ࡢ⸆⌮ຠᯝ࡟ᮇᚅࡋࠊ࠿ࡘ┠ⓗ⣽⬊ࡸᮍศ໬⣽⬊࡜㐺⏝㒊఩࡜ࡢ㝸㞳ࢆ┠ⓗࡍࡿሙྜࠊ㠀⣽⬊ᡂศࡢᔂቯ➼࡟ࡼࡾ⣽⬊➼ࡀ₃ฟࡋ࡞࠸ࡇ࡜ࠋ
 ⣽⬊࡟㑇ఏᏊᕤᏛⓗᨵኚࢆຍ࠼ࡿሙྜ
⣽⬊࡟㑇ఏᏊࢆᑟධࡍࡿሙྜࡣࠊḟ࡟ᥖࡆࡿ஦㡯࡟㛵ࡍࡿヲ⣽ࢆ♧ࡍࡇ࡜ࠋ
ձ┠ⓗ㑇ఏᏊࡢᵓ㐀ࠊ⏤᮶ࠊධᡭ᪉ἲࠊࢡ࣮ࣟࢽࣥࢢ᪉ἲ୪ࡧ࡟ࢭ࣭ࣝࣂࣥࢡࡢㄪ〇᪉ἲࠊ⟶⌮᪉ἲཬࡧ᭦᪂᪉ἲ➼࡟㛵ࡍࡿ᝟ሗ

㸫㸫

ղᑟධ㑇ఏᏊࡢᛶ㉁
ճ┠ⓗ㑇ఏᏊ⏘≀ࡢᵓ㐀ࠊ⏕≀άᛶཬࡧᛶ㉁
մ㑇ఏᏊᑟධᵓᡂయࢆస〇ࡍࡿࡓࡵ࡟ᚲせ࡞ࡍ࡭࡚ࡢཎᮦᩱࠊᛶ㉁ཬࡧᡭ㡰㑇ఏᏊᑟධἲ୪ࡧ࡟㑇ఏᏊᑟධ⏝࣋ࢡࢱ࣮ࡢ⏤᮶ࠊᛶ㉁ཬࡧධᡭ᪉ἲ➼յ㑇ఏᏊᑟධᵓᡂయࡢᵓ㐀ࡸ≉ᛶն࣋ࢡࢱ࣮ࡸ㑇ఏᏊᑟධᵓᡂయࢆస〇ࡍࡿࡓࡵࡢ⣽⬊ࡸ࢘࢖ࣝࢫࡢࣂࣥࢡ໬ཬࡧࣂ
ࣥࢡࡢ⟶⌮᪉ἲ
㑇ఏᏊᑟධ⣽⬊ࡢ〇㐀᪉ἲ࡟ࡘ࠸࡚ࡣࠊᖹᡂ ᖺ  ᭶  ᪥௜ࡅ⸆Ⓨ➨   ྕཌ⏕┬⸆ົᒁ㛗㏻▱ࠕ㑇ఏᏊ἞⒪⏝་⸆ရࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟㛵ࡍࡿᣦ㔪࡟ࡘ࠸࡚ࠖ௨ୗࠊࠕ㑇ఏᏊ἞⒪⏝་⸆ရᣦ㔪ࠖ࡜࠸࠺ࠋࡢูῧࠕ㑇ఏᏊ἞⒪⏝་⸆ရࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟㛵ࡍࡿᣦ㔪ࠖ➨  ❶➼ࢆཧ↷ࡍࡿࡇ࡜ࠋࡲࡓࠊྠ㏻▱ࡢูグ࡟‽ࡌ࡚タᐃࡢጇᙜᛶ➼ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
࡞࠾ࠊ㑇ఏᏊ⤌᥮࠼⏕≀➼ࡢ౑⏝➼ࡢつไ࡟ࡼࡿ⏕≀ࡢከᵝᛶࡢ☜ಖ࡟㛵ࡍࡿἲᚊᖹᡂ  ᖺἲᚊ➨  ྕ࡟ᇶ࡙ࡁࠊࠕࣄࢺࡢ⣽⬊➼ࠖⱝࡋࡃࡣࠕศ໬ࡍࡿ⬟ຊࢆ᭷ࡍࡿࠊཪࡣศ໬ࡋࡓ⣽⬊➼࡛࠶ࡗ࡚ࠊ⮬↛᮲௳࡟࠾࠸࡚ಶయ࡟ᡂ⫱ࡋ࡞࠸ࡶࡢࠖ௨እࡢ
⣽⬊ࠊࠕ࢘࢖ࣝࢫࠖཬࡧࠕ࢘࢖ࣟ࢖ࢻࠖ࡟ᑐࡋ࡚㑇ఏᏊᕤᏛⓗᨵኚࢆຍ࠼ࡿሙྜ࡟ࡣࠊ
ู㏵ᡭ⥆ࡁࡀᚲせ࡜࡞ࡿࡢ࡛␃ពࡍࡿࡇ࡜ࠋ
ୖグࡢグ㏙࡟࠿࠿ࢃࡽࡎࠊ᭱᪂ࡢ▱ぢ࡟ᇶ࡙ࡁࠊ⣽⬊࡟ᑟධࡉࢀࡿ㑇ఏᏊࡀࠊ໬Ꮫ
ⓗ࡟ࡶࠊᶵ⬟ⓗ࡟ࡶ᭱⤊〇ရࡢ୍㒊ࢆᵓᡂࡏࡎࠊ〇㐀ᕤ⛬୰ࡢヨ⸆࡜ࡋ࡚౑⏝ࡉࢀࡿ࡜ุ᩿ࡉࢀࡓሙྜࡣࠊ౑⏝ࡢ┠ⓗ࡟㐺࠺ရ㉁ཬࡧᏳ඲ᛶࡀ☜ಖࡉࢀ࡚࠸ࡿࡇ࡜ࢆ᫂ࡽ
࠿࡟ࡍࡿࡇ࡜࡛ࡼ࠸ࠋ
 ⣽⬊࡟ࢱࣥࣃࢡ㉁ࢆᑟධࡍࡿሙྜ
⣽⬊࡟ࢱࣥࣃࢡ㉁ࢆᑟධࡍࡿሙྜࡣࠊḟ࡟ᥖࡆࡿ஦㡯࡟㛵ࡍࡿヲ⣽ࢆ♧ࡍࡇ࡜ࠋ
ձᑟධࢱࣥࣃࢡ㉁ࡢᵓ㐀ࠊ⏤᮶ཬࡧ⏕≀άᛶࠊ≀⌮໬Ꮫⓗᛶ㉁➼ࡢရ㉁≉ᛶղᑟධࢱࣥࣃࢡ㉁ࡢධᡭ᪉ἲࠊ〇㐀᪉ἲࠊရ㉁⟶⌮᪉ἲཬࡧ᭦᪂᪉ἲ➼࡟㛵ࡍࡿ᝟ሗճᑟධࢱࣥࣃࢡ㉁ࡢ⣽⬊࡬ࡢᑟධ᪉ἲ
մࢱࣥࣃࢡ㉁ᑟධࡢࡓࡵ࡟౑⏝ࡉࢀࡿ໬Ꮫ≀㉁➼࡟ࡘ࠸࡚ࡣࠊࡑࡢᵓ㐀ཬࡧ⏕≀άᛶࠊ≀⌮໬Ꮫⓗᛶ㉁➼ࡢရ㉁≉ᛶյࢱࣥࣃࢡ㉁ᑟධయࢆస〇ࡍࡿሙྜ࡟ࡣࡑࡢ〇㐀᪉ἲࠊရ㉁⟶⌮᪉ἲཬࡧ᭦᪂᪉ἲ
➼࡟㛵ࡍࡿ᝟ሗ
նᑟධࢱࣥࣃࢡ㉁ࢆస〇ࡍࡿࡓࡵࡢ⣽⬊ࡢࣂࣥࢡ໬ཬࡧࣂࣥࢡࡢ⟶⌮᪉ἲୖグࡢグ㏙࡟࠿࠿ࢃࡽࡎࠊ⣽⬊࡟ᑟධࡉࢀࡿࢱࣥࣃࢡ㉁ࡀࠊ໬Ꮫⓗ࡟ࡶࠊᶵ⬟ⓗ࡟ࡶ᭱⤊〇ရࡢ୍㒊ࢆᵓᡂࡏࡎࠊ〇㐀ᕤ⛬୰ࡢヨ⸆࡜ࡋ࡚౑⏝ࡉࢀࡿሙྜࡣࠊ౑⏝ࡢ┠ⓗ࡟㐺࠺ရ㉁ཬࡧᏳ඲ᛶࡀ☜ಖࡉࢀ࡚࠸ࡿࡇ࡜ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜࡛ࡼ࠸ࠋ  ⸆๣➼ࡢฎ⌮࡟ࡼࡾ⣽⬊ࡢึᮇ໬ࠊ⬺ศ໬ཪࡣศ໬ㄏᑟࢆ⾜࠺ሙྜ⸆๣➼ࡢฎ⌮࡟ࡼࡾ⣽⬊ࡢึᮇ໬ࠊ⬺ศ໬ཪࡣศ໬ㄏᑟࢆ⾜࠺ሙྜࡣࠊḟ࡟ᥖࡆࡿ஦㡯࡟㛵ࡍࡿヲ⣽ࢆ♧ࡍࡇ࡜ࠋ
ձ┠ⓗ⸆๣➼ࡢᵓ㐀ࠊ⏤᮶ཬࡧ⏕≀άᛶࠊ≀⌮໬Ꮫⓗᛶ㉁➼ࡢရ㉁≉ᛶղ┠ⓗ⸆๣➼ࡢධᡭ᪉ἲࠊ〇㐀᪉ἲࠊရ㉁⟶⌮᪉ἲཬࡧ᭦᪂᪉ἲ➼࡟㛵ࡍࡿ᝟ሗ

㸫㸫

ճ┠ⓗ⸆๣➼࡟ࡼࡿ⣽⬊ฎ⌮ࡢ᪉ἲ  ≀⌮ⓗ᪉ἲ࡟ࡼࡾ⣽⬊ࡢึᮇ໬ࠊ⬺ศ໬ཪࡣศ໬ㄏᑟࢆ⾜࠺ሙྜ≀⌮ⓗ᪉ἲ࡟ࡼࡾ⣽⬊ࡢึᮇ໬ࠊ⬺ศ໬ཪࡣศ໬ㄏᑟࢆ⾜࠺ሙྜࡣࠊࡑࡢ᪉ἲࡢヲ⣽ࢆ♧ࡍࡇ࡜ࠋ  ࢥࣥࣅࢿ࣮ࢩࣙࣥ࡟ࡼࡾ⣽⬊ࡢึᮇ໬ࠊ⬺ศ໬ཪࡣศ໬ㄏᑟࢆ⾜࠺ሙྜ㑇ఏᏊᕤᏛⓗᨵኚࠊࢱࣥࣃࢡ㉁ᑟධࠊ⸆๣ฎ⌮ཬࡧ≀⌮ⓗ᪉ἲࡢ࠺ࡕࠊ」ᩘࡢ᪉ἲ
ࡢࢥࣥࣅࢿ࣮ࢩࣙࣥ࡟ࡼࡾ⣽⬊ࡢึᮇ໬ࠊ⬺ศ໬ཪࡣศ໬ㄏᑟࢆ⾜࠺ሙྜࡣࠊࡑࡢ᪉ἲࡢヲ⣽ࢆ♧ࡍࡇ࡜ࠋ㸱 ࣄࢺ 㸦ᵝ㸧⣽⬊ᰴࡢᶞ❧
ࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴࡢᶞ❧࡟ᙜࡓࡗ࡚ࡣࠊࢻࢼ࣮ࡢ㑇ఏⓗ⫼ᬒࢆྍ⬟࡞⠊ᅖ࡛⌮ゎࡋࡓ࠺࠼࡛ᶞ❧ࡍࡿࡇ࡜ࠋཎᮦᩱ࡜࡞ࡿయ⣽⬊࠿ࡽ & 㸦ᵝ㸧⣽⬊ᰴᶞ❧ࡲ࡛ࡢ᪉ἲ㸦ࣄࢺయ⣽⬊ࢆᚓࡿࡓࡵࡢ᪉ἲࠊయ⣽⬊ࡢศ㞳࣭ᇵ㣴ࠊయ⣽⬊ࡢึᮇ໬⬺ศ໬ࠊึᮇ໬⬺ศ໬⣽⬊ࡢศ㞳ཬࡧᰴ໬ࡢ᪉ἲࠊࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴᶞ❧ࡲ࡛ࡢྛẁ㝵࡛ࡢᇵᆅࠊᇵ㣴᮲௳ࠊᇵ㣴ᮇ㛫ཬࡧ཰⋡➼㸧ࢆ᫂☜࡟ࡋࠊྍ⬟࡞⠊ᅖ࡛ࡑࡢጇᙜᛶࢆ
᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
ࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴࡢရ㉁ࡢᆒ㉁ᛶཬࡧᏳᐃᛶࢆಖᣢࡍࡿࡓࡵࠊྛ✀⣽⬊≉ᛶᣦᶆ౛࠼ࡤ⣽⬊⣧ᗘࠊᙧែᏛⓗホ౯ࠊ ࢱ࢖ࣆࣥࢢࠊ⾲⌧ᆺ≉␗ⓗ࣐࣮࣮࢝ࠊ᰾ᆺࠊ ࣇ࢕࣮ࣥ࢞ࣉࣜࣥࢸ࢕ࣥࢢࠊ⣽⬊ቑṪ≉ᛶࠊከศ໬⬟࡞࡝ࡢ࠺ࡕ࠿ࡽ㔜せ⣽⬊≉ᛶᣦᶆࢆྠᐃࡋ࡚ࡑࡢᇶ‽ࢆタᐃࡍࡿ࡜࡜ࡶ࡟ࠊタᐃࡉࢀࡓᇶ‽࡟ࡼࡿရ㉁ࢆ⥔ᣢࡋࡓࡲࡲቑṪࡀྍ⬟࡞⥅௦ᩘཪࡣศ⿣ᅇᩘࢆ♧ࡍࡇ࡜ࠋ㸲 ࣄࢺ 㸦ᵝ㸧⣽⬊ᰴࡢಖᏑཬࡧ㐠ᦙ᪉ἲࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴ࡟ࡘ࠸࡚ࠊಖᏑ࣭ὶ㏻ᮇ㛫ཬࡧಖᏑᙧែࢆ༑ศ⪃៖ࡋ࡚ࠊ⣽⬊ࡢ⏕Ꮡ⋡ཬࡧຊ౯➼࡟ᇶ࡙ࡃ㐺ษ࡞Ᏻᐃᛶヨ㦂ࢆᐇ᪋ࡋࠊ㈓ἲཬࡧ᭷ຠᮇ㝈ࢆタᐃࡋࠊࡑࡢጇᙜᛶࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ≉࡟෾⤖ಖ⟶ཬࡧゎ෾ࢆ⾜࠺ሙྜ࡟ࡣࠊ෾⤖ཬࡧゎ෾᧯స࡟ࡼࡿ⣽⬊ᰴࡢᏳᐃᛶࡸつ᱁࡬ࡢᙳ㡪ࡀ࡞࠸࠿ࢆ☜ㄆࡍࡿࡇ࡜ࠋࡲࡓࠊᚲ
せ࡟ᛂࡌ࡚ᶆ‽ⓗ࡞ಖᏑᮇ㛫ࢆ㉸࠼ࡿ㛗ᮇಖᏑ࡟ࡘ࠸࡚ࡶ᳨ウࡋࠊᏳᐃᛶࡢ㝈⏺ࢆྍ⬟࡞⠊ᅖ࡛☜ㄆࡍࡿࡇ࡜ࠋࡓࡔࡋࠊ⣽⬊ᰴࢆᶞ❧ᚋ┤ࡕ࡟౑⏝ࡍࡿࡼ࠺࡞ሙྜࡣࡇࡢ
㝈ࡾ࡛ࡣ࡞࠸ࠋ
ࡲࡓࠊࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴࢆ㐠ᦙࡍࡿሙྜ࡟ࡣࠊ㐠ᦙᐜჾཬࡧ㐠ᦙᡭ㡰 ᗘ⟶⌮➼ࢆྵࡴ➼ࢆᐃࡵࠊࡑࡢጇᙜᛶ࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ㸳 グ㘓ࡢసᡂཬࡧಖ⟶᪉ἲ㸰㹼㸲࡟㛵ࡍࡿ஦㡯࡟ࡘ࠸࡚ࠊᐇ᪋ࡢグ㘓ࢆᩥ᭩࡛సᡂࡋࠊ㐺ษ࡟ಖ⟶ࡍࡿ᪉ἲ࡟
ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
➨㸰 〇㐀ᕤ⛬
ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢ〇㐀࡟ᙜࡓࡗ࡚ࡣࠊ〇㐀᪉ἲࢆ᫂☜࡟ࡋࠊྍ⬟࡞⠊ᅖ࡛ࡑࡢጇᙜᛶࢆ௨ୗࡢ㡯┠᳨࡛ドࡋࠊရ㉁ࡢ୍ᐃᛶࢆಖᣢࡍࡿࡇ࡜ࠋ

㸫㸫

㸯 ࣟࢵࢺᵓᡂࡢ᭷↓࡜ࣟࢵࢺࡢつᐃ᭱⤊〇ရཬࡧ୰㛫〇ရࡀࣟࢵࢺࢆᵓᡂࡍࡿ࠿ྰ࠿ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋࣟࢵࢺࢆᵓ
ᡂࡍࡿሙྜ࡟ࡣࠊࣟࢵࢺࡢෆᐜ࡟ࡘ࠸࡚つᐃࡋ࡚࠾ࡃࡇ࡜ࠋ
㸰 〇㐀᪉ἲ
ཎᮦᩱ࡜࡞ࡿ⣽⬊࣭⤌⧊ࡸయ⣽⬊ࡢཷࡅධࢀ࠿ࡽࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴࡢᶞ❧ཬࡧศ໬ẁ㝵ࡢ㐍ࢇࡔ⣽⬊ࢆ⤒࡚᭱⤊〇ရ࡟⮳ࡿ〇㐀ࡢ᪉ἲࡢᴫせࢆ♧ࡍ࡜࡜ࡶ࡟ࠊලయ
ⓗ࡞ฎ⌮ෆᐜཬࡧᚲせ࡞ᕤ⛬⟶⌮ࠊရ㉁⟶⌮ࡢෆᐜࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
ཷධ᳨ᰝ
ཎᮦᩱ࡜࡞ࡿ⣽⬊࣭⤌⧊ࡸయ⣽⬊ࠊࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴ࡟ࡘ࠸࡚ࠊ⣽⬊࣭⤌⧊ࡢ✀㢮ࡸ౑⏝┠ⓗ࡟ᛂࡌ࡚ᐇ᪋ࡍࡿཷධࡢࡓࡵࡢヨ㦂᳨ᰝࡢ㡯┠౛࠼ࡤࠊ┠ど᳨ᰝࠊ㢧ᚤ㙾᳨ᰝࠊ᥇ྲྀ཰⋡ࠊ⏕Ꮡ⋡ࠊ⣽⬊ࡢ≉ᛶゎᯒཬࡧᚤ⏕≀ヨ㦂➼࡜ྛ㡯┠ࡢุᐃᇶ‽ࢆタᐃࡍࡿࡇ࡜ࠋ἞㦂㛤ጞ๓ẁ㝵࡟࠶ࡗ࡚ࡣࠊࡑࢀࡲ࡛࡟ᚓࡽࢀࡓヨ㦂᳨య࡛ࡢᐇ ್ࢆᥦ♧ࡋࠊࡇࢀࡽࢆ㋃ࡲ࠼ࡓᬻᐃ್ࢆ♧ࡍࡇ࡜ࠋ
⣽⳦ࠊ┿⳦ཬࡧ࢘࢖ࣝࢫ➼ࡢ୙ά໬࣭㝖ཤཎᮦᩱ࡜࡞ࡿ⣽⬊࣭⤌⧊ࠊࣄࢺయ⣽⬊࠶ࡿ࠸ࡣࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴ࡟ࡘ࠸࡚ࠊ
ࡑࡢ⣽⬊⏕Ꮡ⋡ࡸ⾲⌧ᆺࠊ㑇ఏᙧ㉁ཬࡧ≉᭷ࡢᶵ⬟ࡑࡢ௚ࡢ≉ᛶཬࡧရ㉁࡟ᙳ㡪ࢆཬࡰࡉ࡞࠸⠊ᅖ࡛ࠊᚲせ࠿ࡘྍ⬟࡞ሙྜࡣ⣽⳦ࠊ┿⳦ཬࡧ࢘࢖ࣝࢫ➼ࢆ୙ά໬ཪࡣ
㝖ཤࡍࡿฎ⌮ࢆ⾜࠺ࡇ࡜ࠋᙜヱฎ⌮࡟㛵ࡍࡿ᪉⟇࡜ホ౯᪉ἲ࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿ
ࡇ࡜ࠋ⤌⧊ࡢ⣽ษࠊ⣽⬊ࡢศ㞳ࠊ≉ᐃ⣽⬊ࡢ༢㞳➼᥇ྲྀࡋࡓ⣽⬊࣭⤌⧊࠿ࡽ〇ရࢆ〇㐀ࡍࡿึᮇࡢ㐣⛬࡛⾜ࢃࢀࡿ⤌⧊ࡢ⣽ษࠊ&㸦ᵝ㸧⣽⬊ࢆస〇ࡍࡿࡓࡵࡢయ⣽⬊ࡢศ㞳ࠊ≉ᐃయ⣽⬊ࡢ༢㞳ཬࡧࡑࢀࡽࡢὙί➼ࡢ᪉ἲࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ≉ᐃయ⣽⬊ࡢ༢㞳ࢆ⾜࠺ሙྜ࡟ࡣࠊࡑࡢ☜ㄆ᪉ἲࢆタᐃࡍࡿࡇ࡜ࠋ
ࣄࢺ 㸦ᵝ㸧⣽⬊ᰴࡢᶞ❧
ࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴࡢᶞ❧࡟ᙜࡓࡗ࡚ࡣࠊࢻࢼ࣮ࡢ㑇ఏⓗ⫼ᬒࢆྍ⬟࡞⠊ᅖ࡛⌮ゎࡋࡓ࠺࠼࡛ᶞ❧ࡍࡿࡇ࡜ࠋཎᮦᩱ࡜࡞ࡿయ⣽⬊࠿ࡽ & 㸦ᵝ㸧⣽⬊ᰴᶞ❧ࡲ࡛ࡢ᪉ἲࢆ᫂☜࡟ࡋࠊྍ⬟࡞⠊ᅖ࡛ࡑࡢጇᙜᛶࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋࡲࡓࠊ㔜せ⣽⬊≉ᛶᣦᶆࢆྠᐃࡋ࡚ࡑࡢᇶ‽ࢆタᐃࡍࡿ࡜࡜ࡶ࡟ࠊタᐃࡉࢀࡓᇶ‽࡟ࡼࡿရ㉁ࢆ⥔ᣢࡋࡓࡲࡲቑṪࡀྍ⬟࡞⥅௦ᩘཪࡣศ⿣ᅇᩘࢆ♧ࡍࡇ࡜㸦➨㸰❶➨㸯ࡢ㸱ࢆཧ↷㸧ࠋ ࣄࢺ 㸦ᵝ㸧⣽⬊⏤᮶ࡢ୰㛫⣽⬊ᰴࡢᶞ❧୰㛫〇ရ࡜ࡋ࡚ࡢ⣽⬊ᰴ㸦୰㛫⣽⬊ᰴ㸧ࢆᶞ❧ࡍࡿࡇ࡜ࡀࠊᏳ඲࡞᭱⤊┠ⓗ〇ရࢆᏳᐃⓗ࡟〇㐀ࡍࡿୖ࡛㔜せ࡛ࡴࡋࢁ⛉Ꮫⓗ࡟ྜ⌮ⓗ࡞ሙྜࡀ⪃࠼ࡽࢀࡿࠋࡑࡢࡼ
࠺࡞᪉⟇ࢆ㑅ᢥࡋࡓሙྜࡣࠊࡑࡢ฼Ⅼ࡜ጇᙜᛶࢆㄝ᫂ࡋ࡚࠾ࡃࡇ࡜ࠋูࡢ⾲⌧ᆺࢆ♧ࡍ⣽⬊ᰴࢆẁ㝵ⓗ࡟ᶞ❧ࡍࡿ㝿ࡣࠊࡑࢀࡒࢀࡢ⣽⬊ᰴᶞ❧ࡲ࡛ࡢ᪉ἲ㸦ศ໬ㄏᑟ᪉ἲࠊ┠ⓗ࡜ࡍࡿ⣽⬊ࡢศ㞳࣭ᇵ㣴ཬࡧᰴ໬ࡢ᪉ἲࠊ⣽⬊ᰴᶞ❧ࡲ࡛ࡢྛẁ㝵࡛ࡢᇵᆅࠊᇵ㣴᮲௳ࠊᇵ㣴ᮇ㛫ཬࡧ཰⋡➼㸧ࢆ᫂☜࡟ࡋࠊྍ⬟࡞⠊ᅖ࡛ࡑࡢጇᙜᛶࢆ᫂
ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
୰㛫⣽⬊ᰴࡢရ㉁ࡢᆒ㉁ᛶཬࡧᏳᐃᛶࢆಖᣢࡍࡿࡓࡵࠊྛ✀⣽⬊≉ᛶゎᯒᣦᶆ౛࠼ࡤ⣽⬊⣧ᗘࠊᙧែᏛⓗホ౯ࠊ⾲⌧ᆺ≉␗ⓗ࣐࣮࣮࢝ࠊ᰾ᆺࠊ⣽⬊ቑṪ≉ᛶࠊ
㸫㸫

ศ໬⬟࡞࡝ࡢ࠺ࡕ࠿ࡽ㔜せ⣽⬊≉ᛶᣦᶆࢆྠᐃࡋ࡚ࡑࡢᇶ‽ࢆタᐃࡍࡿ࡜࡜ࡶ࡟ࠊタᐃࡉࢀࡓᇶ‽࡟ࡼࡿရ㉁ࢆ⥔ᣢࡋࡓࡲࡲቑṪࡀྍ⬟࡞⥅௦ᩘཪࡣศ⿣ᅇᩘࢆ
♧ࡍࡇ࡜ࠋ᳨ウ࡟㝿ࡋ࡚ࡣࠊ⣽⬊ࡢ㔞ⓗไ㝈ࡸᢏ⾡ⓗ㝈⏺ࡶ࠶ࡾࠊྍ⬟࡞⠊ᅖ࡛⪃៖ࡍࢀࡤⰋ࠸ࠋ
࡞࠾ࠊࡇࡢࡼ࠺࡟ᶞ❧ࡋࡓ୰㛫⣽⬊ᰴࢆࣂࣥࢡ໬ࡋ࡚ά⏝ࡍࡿሙྜࡶ⪃࠼ࡽࢀࡿࡀࠊࡑࡢ㝿ࡣࠊ ࢆཧ↷ࡍࡿࡇ࡜ࠋ ᭱⤊〇ရࡢᵓᡂせ⣲࡜࡞ࡿ⣽⬊ࡢస〇
ࣄࢺ & 㸦ᵝ㸧⣽⬊ᰴ࠿ࡽ┤᥋ࠊ࠶ࡿ࠸ࡣࣄࢺ & 㸦ᵝ㸧⣽⬊⏤᮶୰㛫⣽⬊ᰴࢆ⤒࡚ࠊ᭱⤊〇ရࡢᵓᡂせ⣲࡜࡞ࡿ⣽⬊ࢆస〇ࡍࡿ᪉ἲ㸦ศ໬ㄏᑟ᪉ἲࠊ┠ⓗ࡜ࡍࡿ⣽⬊ࡢศ㞳࣭ᇵ㣴ࡢ᪉ἲࠊᇵ㣴ࡢྛẁ㝵࡛ࡢᇵᆅࠊᇵ㣴᮲௳ࠊᇵ㣴ᮇ㛫ཬࡧ཰⋡➼㸧ࢆ᫂☜࡟ࡋࠊྍ⬟࡞⠊ᅖ࡛ࡑࡢጇᙜᛶࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ ⣽⬊ࡢࣂࣥࢡ໬
ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢ〇㐀ࡢ࠸ࡎࢀ࠿ࡢ㐣⛬࡛ࠊ⣽⬊ࢆࣂࣥࢡ໬ࡍ
ࡿሙྜ࡟ࡣࠊࡑࡢ⌮⏤ࠊࢭ࣭ࣝࣂࣥࢡࡢస〇᪉ἲཬࡧࢭ࣭ࣝࣂࣥࢡࡢ≉ᛶゎᯒࠊಖᏑ࣭⥔ᣢ࣭⟶⌮᪉ἲ࣭᭦᪂᪉ἲࡑࡢ௚ࡢྛసᴗᕤ⛬ࡸヨ㦂࡟㛵ࡍࡿᡭ㡰➼࡟ࡘ࠸࡚ヲ⣽ࢆ᫂ࡽ࠿࡟ࡋࠊጇᙜᛶࢆ♧ࡍࡇ࡜ࠋᖹᡂ  ᖺ ᭶  ᪥௜ࡅ་⸆ᑂ➨  ྕཌ⏕┬་⸆Ᏻ඲ᒁᑂᰝ⟶⌮ㄢ㛗㏻▱ࠕ⏕≀⸆ရࣂ࢖࢜ࢸࢡࣀࣟࢪ࣮ᛂ⏝་⸆ရ㸭⏕≀㉳※⏤᮶་⸆ရ〇㐀⏝⣽⬊ᇶ๣ࡢ⏤᮶ࠊㄪ〇ཬࡧ≉ᛶゎᯒ࡟ࡘ࠸࡚ࠖ➼ࢆཧ⪃࡜ࡍࡿࡇ࡜ࠋࡓࡔࡋࠊࡼࡾୖὶࡢ㐣⛬࡛ホ౯ࡉࢀ࡚࠸ࡿࡇ࡜࡟㉳ᅉࡍࡿṇᙜ࡞⌮⏤࡟ࡼࡾ᳨ウ஦㡯ࡢ୍㒊ࢆ┬␎ࡍࡿࡇ࡜ࡣᕪࡋᨭ࠼࡞࠸ࠋ
 〇㐀ᕤ⛬୰ࡢྲྀࡾ㐪࠼ཬࡧࢡࣟࢫࢥࣥࢱ࣑ࢿ࣮ࢩࣙࣥ㜵Ṇᑐ⟇
ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢ〇㐀࡟࠶ࡓࡗ࡚ࡣࠊ〇㐀ᕤ⛬୰ࡢྲྀࡾ㐪࠼ཬࡧࢡࣟࢫࢥࣥࢱ࣑ࢿ࣮ࢩࣙࣥࡢ㜵Ṇࡀ㔜せ࡛࠶ࡾࠊᕤ⛬⟶⌮࡟࠾ࡅࡿ㜵Ṇᑐ⟇ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ㸱 ᭱⤊〇ရࡢᵓᡂせ⣲࡜࡞ࡿ⣽⬊ࡢ≉ᛶゎᯒ᭱⤊〇ရࡢᵓᡂせ⣲࡜࡞ࡿ⣽⬊࡟ࡘ࠸࡚ࡣࠊ౛࠼ࡤࠊᮍศ໬⣽⬊ࡢΰධࡸ┠ⓗእࡢ⣽⬊ࡢΰධࢆつᐃࡍࡿࡓࡵࡢ⣽⬊⣧ᗘࢆࡣࡌࡵ࡜ࡋ࡚ࠊ⣽⬊⏕Ꮡ⋡ࠊᙧែᏛⓗ≉ᚩࠊ⣽⬊ቑṪ≉ᛶࠊ⏕໬Ꮫⓗᣦᶆࠊච␿Ꮫⓗᣦᶆࠊ≉ᚩⓗ⏘⏕≀㉁ࠊ᰾ᆺࠊศ໬⬟ࡑࡢ௚㐺ษ࡞㑇ఏᆺཪࡣ⾲⌧ᆺࡢᣦᶆࢆゎᯒࡍࡿ࡜࡜ࡶ࡟ࠊᚲせ࡟ᛂࡌ࡚ᶵ⬟ゎᯒࢆ⾜࠺ࡇ࡜ࠋࡲࡓࠊᇵ㣴ᮇ㛫ࡢጇᙜᛶཬࡧ⣽⬊ࡢᏳᐃᛶࢆホ౯ࡍࡿࡓࡵ࡟ࠊணᐃࡢᇵ㣴ᮇ㛫ࢆ㉸࠼࡚ᇵ㣴ࡋࡓ⣽⬊࡟࠾࠸࡚┠ⓗእࡢኚ໬ࡀ࡞࠸ࡇ࡜ࢆ㐺ษ࡞⣽⬊≉ᛶᣦᶆ➼ࢆ⏝࠸࡚♧ࡍࡇ࡜ࠋࡇࢀࡽࡢ᳨ウ࡟㝿ࡋ࡚ࡣࠊ࠶ࡽ࠿ࡌࡵヨ㦂ⓗ᳨యࢆ⏝࠸ࡓ᳨ウ࡟ࡼࡗ࡚ᐇ᪋᳨࣭ドࡋ࡚࠾ࡃࡇ࡜࡛ࡶⰋ࠸ࡀࠊࡇࢀࡽࡢ᳨ウ⤖ᯝ࠿ࡽᝈ⪅࡟〇ရࢆ㐺⏝ࡍࡿ㝿࡟㑅ᢥࡍ࡭ࡁ㔜せ⣽⬊≉ᛶᣦᶆࢆ᫂ࡽ࠿࡟ࡋ࡚࠾ࡃࡇ࡜ࠋ᳨ウ࡟㝿ࡋ࡚ࡣࠊ᳨యࡢ
㔞ⓗไ㝈ࡸᢏ⾡ⓗ㝈⏺ࡶ࠶ࡾࠊྍ⬟࡞⠊ᅖ࡛⪃៖ࡍࢀࡤࡼ࠸ࠋ㐺⏝ᚋ࡟యෆ࡛ࡢቑṪ➼ࢆᮇᚅࡍࡿሙྜ࡟ࡣࠊタᐃࡉࢀࡓᇶ‽࡟ࡼࡿ⥅௦ᩘཪࡣศ⿣ᅇᩘ࡛ᮇᚅࡉࢀࡓᶵ⬟
ࢆⓎ᥹ࡍࡿࡇ࡜ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ㸲 ᭱⤊〇ရࡢᙧែࠊໟ⿦

㸫㸫

᭱⤊〇ရࡢᙧែࠊໟ⿦ࡣࠊ〇ရࡢရ㉁ࢆ☜ಖ࡛ࡁࡿࡶࡢ࡛࡞ࡅࢀࡤ࡞ࡽ࡞࠸ࠋ㸳 〇ရࡢಖᏑཬࡧ㐠ᦙ୰㛫〇ရཪࡣ᭱⤊〇ရࢆಖᏑཬࡧ㐠ᦙࡍࡿᚲせࡀ࠶ࡿሙྜ࡟ࡣࠊಖᏑ᪉ἲࡸᮇ㛫ཬࡧ㐠ᦙᐜჾࠊ㐠ᦙᡭẁ㸦 ᗘ⟶⌮➼ࢆྵࡴࠋ㸧ࢆᐃࡵࠊࡑࡢጇᙜᛶࢆ᫂ࡽ࠿࡟ࡍࡿࡇ
࡜㸦➨㸱❶ཧ↷㸧ࠋ㸴 〇㐀᪉ἲࡢᜏᖖᛶ
ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢ〇㐀࡟ᙜࡓࡗ࡚ࡣࠊ〇㐀ᕤ⛬ࢆ㏻ࡌ࡚ࠊಶู࡟ຍᕤࡋࡓ〇ရࡢ⣽⬊ᩘࠊ⣽⬊⏕Ꮡ⋡୪ࡧ࡟〇ရࡢ౑⏝┠ⓗཬࡧ㐺⏝᪉ἲ➼࠿ࡽࡳࡓ≉ᚩ⾲⌧ᆺࡢ㐺ษ࡞ᣦᶆࠊ㑇ఏᆺࡢ㐺ษ࡞ᣦᶆࠊᶵ⬟≉ᛶཬࡧ┠ⓗ࡜ࡍࡿ⣽⬊ࡢྵ᭷⋡➼ࡀ〇ရࣟࢵࢺ㛫࡛ᮏ㉁ⓗ࡟ᦆ࡞ࢃࢀ࡞࠸ࡇ࡜ࢆࠊ࠶ࡽ࠿ࡌࡵホ౯ࡋ࡚࠾ࡃࡇ
࡜ࠋࡇࡢ㝿ࠊヨ㦂ⓗ᳨యࢆ⏝࠸࡚ࡶⰋ࠸ࠋࡲࡓࠊ୰㛫〇ရ࡛ホ౯ࡍࡿࡇ࡜ࡀࠊཎᮦᩱ
࡜ࡋ࡚ࡢ⣽⬊࣭⤌⧊ࡢ㐺᱁ᛶࡸ୰㛫〇ရࡲ࡛ࡢ〇㐀㐣⛬ࡢጇᙜᛶࢆࡼࡃ཯ᫎࡋࠊࡲࡓࠊ
᭱⤊〇ရ࡟ྥࡅ࡚ࡢ㐺ṇ࡞㐨ᶆ࡜࡞ࡿ࡞࡝ࠊྜ⌮ⓗ࡞ሙྜࡶ࠶ࡿࡢ࡛ࠊᚲせ࡟ᛂࡌ࡚㑅ᢥ⫥࡜ࡍࡿࡇ࡜ࠋ
〇㐀ᕤ⛬୰ࡢ෾⤖ಖᏑᮇ㛫ࡸຍᕤ࡟క࠺⣽⬊ᇵ㣴ࡢᮇ㛫ࡀ㛗ᮇ࡟ཬࡪሙྜ࡟ࡣ୍
ᐃᮇ㛫ࡈ࡜࡟↓⳦ヨ㦂ࢆ⾜࠺࡞࡝ࠊ↓⳦ᛶࡀ☜ಖࡉࢀࡿࡇ࡜ࢆ☜ㄆࡍࡿࡇ࡜ࠋ㸵 〇㐀᪉ἲࡢኚ᭦
㛤Ⓨ㏵୰࡟〇㐀᪉ἲࢆኚ᭦ࡋࡓሙྜࠊኚ᭦๓ࡢ〇㐀᪉ἲ࡟ࡼࡿ〇ရࢆ⏝࠸࡚ᚓࡓヨ㦂ᡂ⦼ࢆ἞㦂㛤ጞ᫬ཪࡣᢎㄆ⏦ㄳ࡟౑⏝ࡍࡿ࡜ࡁࡣࠊ〇㐀᪉ἲኚ᭦๓ᚋࡢ〇ရࡢྠ➼ᛶ㸭ྠ㉁ᛶࢆ♧ࡍࡇ࡜ࠋ➨㸱 ᭱⤊〇ရࡢရ㉁⟶⌮㸯 ⥲ㄽ
ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢရ㉁⟶⌮඲యࡢ᪉⟇࡜ࡋ࡚ࡣࠊ᭱⤊〇ရࡢつ᱁ཬࡧヨ㦂᪉ἲࡢタᐃࠊಶูᝈ⪅࡬ࡢ㐺⏝ࡈ࡜ࡢཎᮦᩱࡢရ㉁⟶⌮ࠊ〇㐀ᕤ⛬ࡢጇᙜᛶࡢ᳨ド࡜୍ᐃᛶࡢ⥔ᣢ⟶⌮ࡢ࡯࠿ࠊ୰㛫〇ရࡢရ㉁⟶⌮ࢆ㐺ṇ࡟⾜࠺ࡇ࡜➼ࡀᣲࡆࡽࢀࡿࠋ
ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼࡟࠾࠸࡚ࡣ┠ⓗ⣽⬊௨እࡢᮍศ໬⣽⬊ࡢΰධࢆྰ
ᐃࡍࡿࡓࡵࡢ᪉⟇ࡀ᭱ࡶ㔜せ࡞せ௳ࡢ୍ࡘ࡛࠶ࡿࠋྍ⬟࡞㝈ࡾ୰㛫〇ရࡢẁ㝵࡛┠ⓗ⣽⬊௨እࡢᮍศ໬⣽⬊ࡢΰධࢆྰᐃࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ
᭱⤊〇ရࡢつ᱁ཬࡧヨ㦂᪉ἲ࡟ࡘ࠸࡚ࡣࠊᑐ㇟࡜ࡍࡿ⣽⬊࣭⤌⧊ࡢ✀㢮ཬࡧᛶ㉁ࠊ
〇㐀᪉ἲࠊྛ〇ရࡢ⮫ᗋ౑⏝┠ⓗࡸ౑⏝᪉ἲࠊᏳᐃᛶࠊ฼⏝ྍ⬟࡞ヨ㦂ἲ➼࡟ࡼࡗ࡚␗࡞ࡿ࡜⪃࠼ࡽࢀࡿࡓࡵࠊྲྀࡾᢅ࠺⣽⬊࣭⤌⧊࡟ࡼࡗ࡚ࡇࢀࡽࡢ㐪࠸ࢆ༑ศ࡟⪃៖ࡋ࡚タᐃࡍࡿࡇ࡜ࠋࡲࡓࠊ〇㐀ᕤ⛬ࡢጇᙜᛶࡢ᳨ド࡜୍ᐃᛶࡢ⥔ᣢ⟶⌮ἲࠊ୰㛫〇ရࡢရ㉁⟶⌮➼࡜ࡢ┦஫⿵᏶㛵ಀࢆ⪃៖࡟ධࢀ࡚ࠊ඲య࡜ࡋ࡚ရ㉁⟶⌮ࡢ┠ⓗࡀ㐩ᡂࡉࢀࡿ࡜ࡢほⅬ࠿ࡽࠊྜ⌮ⓗ࡟つ᱁ཬࡧヨ㦂᪉ἲࢆタᐃࡋࠊࡑࡢ᰿ᣐࢆ♧ࡍࡇ࡜ࠋ࡞࠾ࠊ
἞㦂㛤ጞ๓ࡢホ౯ࡣࠊ἞㦂ࢆᐇ᪋ࡍࡿ〇ရࡢရ㉁࡜ࡋ࡚ၥ㢟ࡀ࡞࠸࡜ࡳ࡞ࡏࡿࡇ࡜ࢆ

㸫㸫

☜ㄆࡍࡿࡇ࡜ࢆ┠ⓗ࡜ࡋ࡚࠸ࡿࠋࡋࡓࡀࡗ࡚ࠊ↓⳦ᛶࡸ࣐࢖ࢥࣉࣛࢬ࣐ࡢྰᐃ࡞࡝ᚲ
㡲࡞ࡶࡢࢆ㝖ࡁࠊ἞㦂ᚋ࡟⮫ᗋヨ㦂ᡂ⦼࡜ရ㉁ࡢ㛵ಀࢆㄽࡎࡿࡓࡵ࡟ᚲせ࡞ရ㉁≉ᛶ࡟ࡘ࠸࡚ࡣࠊࡸࡴࢆᚓ࡞࠸ሙྜࡣᑡᩘࡢヨ㦂ⓗ᳨యࡢᐇ ್ࢆࡶ࡜࡟ࡑࡢኚືࢆࡋ࠿
ࡿ࡭ࡁ⠊ᅖෆ࡟タᐃࡍࡿᬻᐃⓗ࡞つ᱁ཬࡧヨ㦂᪉ἲࢆタᐃࡍࡿࡇ࡜࡛ᕪࡋᨭ࠼࡞࠸ࠋ
ࡓࡔࡋࠊつ᱁ཬࡧヨ㦂᪉ἲࢆྵࡴရ㉁⟶⌮ἲࡣ἞㦂ࡢ㐍⾜࡜࡜ࡶ࡟඘ᐇ࣭ᩚഛࢆᅗࡿࡇ࡜ࠋ㸰 ᭱⤊〇ရࡢရ㉁⟶⌮ἲ᭱⤊〇ရ࡟ࡘ࠸࡚ࠊ௨ୗ࡟♧ࡍ୍⯡ⓗ࡞ရ㉁⟶⌮㡯┠ཬࡧヨ㦂ࢆཧ⪃࡜ࡋ࡚ࠊᚲせ࡛㐺ษ࡞つ᱁ཬࡧヨ㦂᪉ἲࢆタᐃࡋࠊࡑࡢ᰿ᣐࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
ࣟࢵࢺࢆᵓᡂࡋ࡞࠸〇ရࢆ〇㐀ࡍࡿሙྜࡣಶู〇ရࡈ࡜࡟ࠊࣟࢵࢺࢆᵓᡂࡍࡿ〇ရ
ࢆ〇㐀ࡍࡿሙྜ࡟ࡣࠊ㏻ᖖࠊྛಶู〇ရ࡛ࡣ࡞ࡃྛࣟࢵࢺࡀရ㉁⟶⌮ࡢᑐ㇟࡜࡞ࡿࡢ
࡛ࠊࡇࢀࢆ㋃ࡲ࠼࡚ࡑࢀࡒࢀ㐺ษ࡞つ᱁ࠊヨ㦂᪉ἲࢆタᐃࡍࡿࡇ࡜ࠋ
⣽⬊ᩘ୪ࡧ࡟⏕Ꮡ⋡ᚓࡽࢀࡓ⣽⬊ࡢᩘ࡜⏕Ꮡ⋡ࡣࠊ᭱⤊〇ရཪࡣᚲせ࡟ᛂࡌ࡚㐺ษ࡞〇㐀ᕤ⛬ࡢ〇ရ࡛ ᐃࡍࡿࡇ࡜ࠋ࡞࠾ࠊ἞㦂㛤ጞ᫬࡟࠾࠸࡚ࡣࠊᑡᩘࡢヨ㦂ⓗ᳨య࡛ࡢᐇ ್ࢆ㋃ࡲ࠼ࡓᬻᐃⓗ࡞つ᱁ࢆタᐃࡍࡿࡇ࡜࡛ࡶⰋ࠸ࠋ
☜ㄆヨ㦂┠ⓗ࡜ࡍࡿ⣽⬊࣭⤌⧊ࡢᙧែᏛⓗ≉ᚩࠊ⏕໬Ꮫⓗᣦᶆࠊච␿Ꮫⓗᣦᶆࠊ≉ᚩⓗ⏘⏕≀㉁ࡑࡢ௚㐺ษ࡞㑇ఏᆺ࠶ࡿ࠸ࡣ⾲⌧ᆺࡢ࠺ࡕࠊ㔜せ⣽⬊≉ᛶᣦᶆࢆ㑅ᢥࡋ࡚ࠊ┠ⓗ࡜ࡍࡿ⣽⬊࡛࠶ࡿࡇ࡜ࢆ☜ㄆࡍࡿࡇ࡜ࠋ
⣽⬊ࡢ⣧ᗘヨ㦂┠ⓗ⣽⬊௨እࡢᮍศ໬⣽⬊ࠊ␗ᖖቑṪ⣽⬊ࠊᙧ㉁㌿᥮⣽⬊ࡢ᭷↓ࡸΰධ⣽⬊ࡢ᭷↓➼ࡢ⣽⬊ࡢ⣧ᗘ࡟ࡘ࠸࡚ࠊ┠ⓗ࡜ࡍࡿ⣽⬊࣭⤌⧊ࡢ⏤᮶ࠊᇵ㣴᮲௳➼ࡢ〇㐀ᕤ⛬ࠊ୰㛫〇ရࡢရ㉁⟶⌮➼ࢆ຺᱌ࡋࠊᚲせ࡟ᛂࡌ࡚ヨ㦂㡯┠ࠊヨ㦂᪉ἲཬࡧุᐃᇶ‽ࢆ♧ࡍࡇ࡜ࠋ࡞࠾ࠊ἞㦂㛤ጞ᫬࡟࠾࠸࡚ࡣࠊᑡᩘࡢヨ㦂ⓗ᳨య࡛ࡢᐇ ್ࢆ㋃ࡲ࠼ࡓ
ᬻᐃⓗ࡞つ᱁ࢆタᐃࡍࡿࡇ࡜࡛ࡶⰋ࠸ࠋ
⣽⬊⏤᮶ࡢ┠ⓗእ⏕⌮άᛶ≀㉁࡟㛵ࡍࡿヨ㦂⣽⬊⏤᮶ࡢྛ✀┠ⓗእ⏕⌮άᛶ≀㉁ࡢ࠺ࡕࠊ〇ရ୰࡛ࡢᏑᅾ㔞ዴఱ࡛ᝈ⪅࡟Ᏻ඲ᛶୖࡢ㔜኱࡞ᙳ㡪ࢆཬࡰࡍྍ⬟ᛶࡀ᫂ࡽ࠿࡟᝿ᐃࡉࢀࡿሙྜ࡟ࡣࠊ㐺ษ࡞チᐜ㔞㝈ᗘヨ㦂ࢆタᐃࡍࡿࡇ࡜ࠋ࡞࠾ࠊ἞㦂㛤ጞ᫬࡟࠾࠸࡚ࡣࠊᑡᩘࡢヨ㦂ⓗ᳨య࡛ࡢᐇ
್ࢆ㋃ࡲ࠼ࡓᬻᐃⓗ࡞つ᱁ࢆタᐃࡍࡿࡇ࡜࡛ࡶⰋ࠸ࠋ
 〇㐀ᕤ⛬⏤᮶୙⣧≀ヨ㦂ཎᮦᩱ࡟Ꮡᅾࡍࡿ࠿ཪࡣ〇㐀㐣⛬࡛㠀⣽⬊ᡂศࠊᇵᆅᡂศ㸦ࣇ࢕࣮ࢲ࣮⣽⬊ࢆྵࡴ㸧ࠊ㈨ᮦࠊヨ⸆➼࡟⏤᮶ࡋࠊ〇ရ୰࡟ΰධ≀ࠊṧ␃≀ࠊཪࡣ᪂ࡓ࡞⏕ᡂ≀ࠊศゎ≀➼࡜ࡋ࡚Ꮡᅾࡍࡿྍ⬟ᛶࡀ࠶ࡿࡶࡢ࡛ࠊ࠿ࡘࠊရ㉁ཬࡧᏳ඲ᛶࡢ㠃࠿ࡽࡳ࡚ᮃࡲ
ࡋࡃ࡞࠸≀㉁➼౛࠼ࡤࠊ࢘ࢩ⫾ඣ⾑Ύ⏤᮶ࡢ࢔ࣝࣈ࣑ࣥࠊᢠ⏕≀㉁➼࡟ࡘ࠸࡚ࡣࠊ
ᙜヱ≀㉁ࡢ㝖ཤ࡟㛵ࡍࡿࣉࣟࢭࢫホ౯ࡸᙜヱ≀㉁࡟ᑐࡍࡿᕤ⛬ෆ⟶⌮ヨ㦂ࡢ⤖ᯝࢆ⪃៖ࡋ࡚ࡑࡢᏑᅾࢆྰᐃࡍࡿ࠿ࠊཪࡣ㐺ษ࡞ヨ㦂ࢆタᐃࡋ࡚Ꮡᅾチᐜ㔞ࢆつᐃࡍࡿࡇ࡜ࠋヨ㦂ᑐ㇟≀㉁ࡢ㑅ᐃཬࡧつ᱁್ࡢタᐃ࡟ᙜࡓࡗ࡚ࡣࠊタᐃࡢጇᙜᛶ࡟ࡘ࠸ 
㸫㸫

࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
࡞࠾ࠊ἞㦂㛤ጞ᫬࡟࠾࠸࡚ࡣࠊᑡᩘࡢヨ㦂ⓗ᳨య࡛ࡢᐇ ್ࢆ㋃ࡲ࠼ࡓᬻᐃⓗ࡞つ᱁ࢆタᐃࡍࡿࡇ࡜࡛ࡶⰋ࠸ࠋ ↓⳦ヨ㦂ཬࡧ࣐࢖ࢥࣉࣛࢬ࣐ྰᐃヨ㦂᭱⤊〇ရࡢ↓⳦ᛶ࡟ࡘ࠸࡚ࡣࠊ࠶ࡽ࠿ࡌࡵヨ㦂ⓗ᳨యࢆ⏝࠸࡚඲〇㐀ᕤ⛬ࢆ㏻ࡌ࡚↓⳦ᛶࢆ☜ಖ࡛ࡁࡿࡇ࡜ࢆ༑ศ࡟ホ౯ࡋ࡚࠾ࡃᚲせࡀ࠶ࡿࠋ᭱⤊〇ရ࡟ࡘ࠸࡚ࠊ
ᝈ⪅࡟㐺⏝ࡍࡿ๓࡟↓⳦ᛶ୍⯡⣽⳦ཬࡧ┿⳦ྰᐃࢆヨ㦂࡟ࡼࡾ♧ࡍࡇ࡜ࠋࡲࡓࠊ
㐺ษ࡞࣐࢖ࢥࣉࣛࢬ࣐ྰᐃヨ㦂ࢆᐇ᪋ࡍࡿࡇ࡜ࠋ࣐࢖ࢥࣉࣛࢬ࣐ྰᐃヨ㦂࡟ࡘ࠸࡚ࡣࠊ᳨ドࡉࢀࡓ᰾㓟ቑᖜἲࢆ⏝࠸ࡿࡇ࡜࡛ࡶࡼ࠸ࠋ᭱⤊〇ရࡢ↓⳦ヨ㦂➼ࡢ⤖ᯝࡀࠊᝈ⪅࡬ࡢᢞ୚ᚋ࡟ࡋ࠿ᚓࡽࢀ࡞࠸ሙྜ࡟ࡣࠊᢞ୚ᚋ࡟↓⳦ᛶ➼ࡀྰᐃࡉࢀࡓሙྜࡢ
ᑐฎ᪉ἲࢆ࠶ࡽ࠿ࡌࡵタᐃࡋ࡚࠾ࡃࡇ࡜ࠋࡲࡓࠊࡇࡢሙྜࠊ୰㛫〇ရ࡛↓⳦ᛶࢆヨ㦂࡟ࡼࡾ♧ࡋࠊ᭱⤊〇ရ࡟⮳ࡿᕤ⛬ࡢ↓⳦ᛶࢆཝᐦ࡟⟶⌮ࡍࡿᚲせࡀ࠶ࡿࠋࡲࡓࠊྠ୍᪋タ࣭ྠ୍ᕤ⛬࡛௨๓࡟௚ࡢᝈ⪅࡬ࡢ㐺⏝౛ࡀ࠶ࡿሙྜ࡟ࡣࠊ඲౛࡟࠾࠸࡚ヨ㦂࡟ࡼࡾ↓⳦ᛶࡀ☜ㄆࡉࢀ࡚࠸ࡿࡇ࡜ࠋࣟࢵࢺࢆᵓᡂࡍࡿ〇ရ࡛ᐦᑒᛶࡀಖドࡉࢀ࡚࠸ࡿሙྜ࡟ࡣࠊ௦⾲౛࡟ࡼࡿヨ㦂࡛ࡼ࠸ࠋ㐺⏝ࡈ࡜࡟ヨ㦂ࢆᐇ᪋ࡍࡿᚲせࡀ࠶ࡿሙྜ࡛ࠊ↓⳦ヨ㦂➼ࡢ⤖ᯝࡀࠊᝈ⪅࡬ࡢᢞ୚ᚋ࡟ࡋ࠿ᚓࡽࢀ࡞࠸ሙྜ࡟ࡣࠊ㐺⏝ࡢྍྰࡣ┤㏆ࡢࢹ࣮ࢱࢆཧ⪃࡟ࡍࡿࡇ࡜࡟࡞ࡿࡀࠊࡇࡢሙྜ࡛ࡶ᭱⤊〇ရࡢ↓⳦ヨ㦂➼ࡣᚲࡎ⾜࠺ࡇ࡜ࠋ
ᢠ⏕≀㉁ࡣ⣽⬊ᇵ㣴⣔࡛ᴟຊ౑⏝ࡋ࡞࠸ࡇ࡜ࡀᮃࡲࢀࡿࡀࠊ౑⏝ࡋࡓሙྜ࡟ࡣࠊ
↓⳦ヨ㦂࡟ᙳ㡪ࢆཬࡰࡉ࡞࠸ࡼ࠺ฎ⨨ࡍࡿࡇ࡜ࠋ ࢚ࣥࢻࢺ࢟ࢩࣥヨ㦂ヨᩱ୰ࡢዃ㞧≀ࡢᙳ㡪ࢆ⪃៖ࡋ࡚ヨ㦂ࢆᐇ᪋ࡍࡿࡇ࡜ࠋつ᱁್ࡣᚲࡎࡋࡶᐇ ್࡟ࡼࡽࡎࠊ᪥ᮏ⸆ᒁ᪉➼࡛♧ࡉࢀ࡚࠸ࡿ᭱⤊〇ရࡢ  ᅇᢞ୚㔞ࢆᇶ࡟ࡋࡓᏳ඲ᇦࢆ
⪃៖ࡋ࡚タᐃࡍࢀࡤࡼ࠸ࠋࡲࡓࠊᕤ⛬ෆ⟶⌮ヨ㦂࡜ࡋ࡚タᐃࡍࡿࡇ࡜ࡶ⪃࠼ࡽࢀࡿࡀࠊࡑࡢሙྜ࡟ࡣࠊࣂࣜࢹ࣮ࢩࣙࣥࡢ⤖ᯝࢆྵࡵ࡚ᇶ‽➼ࢆタᐃࡋࠊࡑࡢጇᙜᛶࢆ
ㄝ᫂ࡍࡿࡇ࡜ࠋ ࢘࢖ࣝࢫヨ㦂ཎᮦᩱ࡞࠸ࡋ〇㐀ᕤ⛬࡟࠾࠸࡚ࣂࣥࢡ໬ࡉࢀ࡚࠾ࡽࡎࠊ࢘࢖ࣥࢻ࢘ࣆࣜ࢜ࢻࡀྰ
ᐃ࡛ࡁࡎࠊ"ࠊ"ࠊ"ࠊ!" ࢆቑṪࡉࡏࡿྍ⬟ᛶࡢ࠶ࡿ⣽⬊ࡢሙྜ࡟ࡣࠊ୰㛫〇ရࠊ᭱⤊〇ရ➼࡟ࡘ࠸࡚ࠊቑṪྍ⬟ᛶࡢ࠶ࡿ࢘࢖ࣝࢫ࡟ࡘ࠸࡚ࡑࡢᏑᅾ㔞࡟㛵ࡍࡿヨ㦂ࢆᐇ᪋ࡋࠊ& 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢᢞ୚ࡀᝈ⪅ࡢ୙฼┈࡟࡞ࡽ࡞࠸ࡇ
࡜ࢆ☜ㄆࡍࡿᚲせࡀ࠶ࡿࠋࡲࡓࠊ〇㐀ᕤ⛬୰࡛⏕≀⏤᮶ᡂศࢆ౑⏝ࡍࡿሙྜ࡟ࡣࠊ
᭱⤊〇ရ࡛ᙜヱᡂศ⏤᮶ࡢ࢘࢖ࣝࢫ࡟ࡘ࠸࡚ࡢྰᐃヨ㦂ࡢᐇ᪋ࢆ⪃៖ࡍ࡭ࡁሙྜ
ࡶ࠶ࡿ࠿ࡶࡋࢀ࡞࠸ࡀࠊྍ⬟࡞㝈ࡾࠊࡶ࡜ࡢᡂศẁ㝵࡛ࡢヨ㦂ࡸࣉࣟࢭࢫホ౯࡛㏞ධࡀྰᐃࡉࢀ࡚࠸ࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ ຠ⬟ヨ㦂⣽⬊✀ࠊ⮫ᗋ౑⏝┠ⓗཪࡣ≉ᛶ➼࡟ᛂࡌࡓ㐺ษ࡞ຠ⬟ヨ㦂ࡢᐇ᪋ࢆ⪃៖ࡍ࡭ࡁሙ
ྜࡶ࠶ࡿࠋ࡞࠾ࠊ἞㦂㛤ጞ᫬࡟࠾࠸࡚ࡣࠊᑡᩘࡢヨ㦂ⓗ᳨య࡟ࡼࡿᐇ ್ࢆ㋃ࡲ࠼
ࡓᬻᐃⓗ࡞つ᱁ࢆタᐃࡍࡿࡇ࡜࡛ࡶⰋ࠸ࠋ
ຊ౯ヨ㦂 
㸫㸫

⣽⬊࣭⤌⧊࠿ࡽศἪࡉࢀࡿ≉ᐃࡢ⏕⌮άᛶ≀㉁ࡢศἪࡀᙜヱࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢຠ⬟ཪࡣຠᯝࡢᮏ㉁࡛࠶ࡿሙྜ࡟ࡣࠊࡑࡢ┠ⓗ࡜ࡋ࡚࠸ࡿᚲせ࡞ຠ
ᯝࢆⓎ᥹ࡍࡿࡇ࡜ࢆ♧ࡍࡓࡵ࡟ࠊᙜヱ⏕⌮άᛶ≀㉁࡟㛵ࡍࡿ᳨ᰝ㡯┠ཬࡧつ᱁ࢆタᐃࡍࡿࡇ࡜ࠋ㑇ఏᏊࢆᑟධࡋࡓሙྜࡢⓎ⌧⏘≀ཪࡣ⣽⬊࠿ࡽศἪࡉࢀࡿ┠ⓗࡢ⏕ᡂ≀➼࡟ࡘ࠸࡚ࠊຊ౯ࠊ⏘⏕㔞➼ࡢつ᱁ࢆタᐃࡍࡿࡇ࡜ࠋ࡞࠾ࠊ἞㦂㛤ጞ࡟࠾࠸࡚ࡣࠊ
ᑡᩘࡢヨ㦂ⓗ᳨య࡟ࡼࡿᐇ ್ࢆ㋃ࡲ࠼ࡓᬻᐃⓗ࡞つ᱁ࢆタᐃࡍࡿࡇ࡜࡛ࡶⰋ࠸ࠋ
ຊᏛⓗ㐺ྜᛶヨ㦂୍ᐃࡢຊᏛⓗᙉᗘࢆᚲせ࡜ࡍࡿ〇ရ࡟ࡘ࠸࡚ࡣࠊ㐺⏝㒊఩ࢆ⪃៖ࡋࡓຊᏛⓗ㐺ྜᛶཬࡧ⪏ஂᛶࢆ☜ㄆࡍࡿࡓࡵࡢつ᱁ࢆタᐃࡍࡿࡇ࡜ࠋ࡞࠾ࠊ἞㦂㛤ጞ᫬࡟࠾࠸࡚ࡣࠊ
ᑡᩘࡢヨ㦂ⓗ᳨య࡟ࡼࡿᐇ ್ࢆ㋃ࡲ࠼ࡓᬻᐃⓗ࡞つ᱁ࢆタᐃࡍࡿࡇ࡜࡛ࡶⰋ࠸ࠋ
➨㸱❶ ࣄࢺ 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢᏳᐃᛶ
〇ရ໬ࡋࡓࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ཪࡣ㔜せ࡞ࡑࢀࡽࡢ୰㛫〇ရ࡟ࡘ࠸࡚ࠊ
ಖᏑ࣭ὶ㏻ᮇ㛫ཬࡧಖᏑᙧែࢆ༑ศ⪃៖ࡋ࡚ࠊ⣽⬊ࡢ⏕Ꮡ⋡ཬࡧຊ౯➼࡟ᇶ࡙ࡃ㐺ษ࡞Ᏻᐃᛶヨ㦂ࢆᐇ᪋ࡋࠊ㈓ἲཬࡧ᭷ຠᮇ㝈ࢆタᐃࡋࠊࡑࡢጇᙜᛶࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ≉࡟෾⤖ಖ⟶ཬࡧゎ෾ࢆ⾜࠺ሙྜ࡟ࡣࠊ෾⤖ཬࡧゎ෾᧯స࡟ࡼࡿ〇ရࡢᏳᐃᛶࡸつ᱁࡬ࡢᙳ㡪ࡀ࡞࠸࠿ࢆ☜ㄆࡍࡿࡇ࡜ࠋࡲࡓࠊᚲせ࡟ᛂࡌ࡚ᶆ‽ⓗ࡞〇㐀ᮇ㛫ࢆ㉸࠼ࡿሙྜࡸᶆ
‽ⓗ࡞ಖᏑᮇ㛫ࢆ㉸࠼ࡿ㛗ᮇಖᏑ࡟ࡘ࠸࡚ࡶ᳨ウࡋࠊᏳᐃᛶࡢ㝈⏺ࢆྍ⬟࡞⠊ᅖ࡛☜ㄆࡍࡿࡇ࡜ࠋࡓࡔࡋࠊ〇ရ໬ᚋ┤ࡕ࡟౑⏝ࡍࡿࡼ࠺࡞ሙྜࡣࡇࡢ㝈ࡾ࡛ࡣ࡞࠸ࠋࡲࡓࠊ〇ရ໬ࡋࡓࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࢆ㐠ᦙࡍࡿሙྜ࡟ࡣࠊ㐠ᦙᐜჾཬࡧ㐠ᦙᡭ㡰 ᗘ⟶⌮➼ࢆྵࡴࠋ➼ࢆᐃࡵࠊࡑࡢጇᙜᛶ࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
➨㸲❶ ࣄࢺ 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢ㠀⮫ᗋᏳ඲ᛶヨ㦂〇ရࡢ≉ᛶཬࡧ㐺⏝ἲ࠿ࡽホ౯ࡀᚲせ࡜⪃࠼ࡽࢀࡿᏳ඲ᛶ㛵㐃஦㡯࡟ࡘ࠸࡚ࠊᢏ⾡ⓗ࡟ྍ⬟࡛࠶ࢀࡤࠊ⛉Ꮫⓗྜ⌮ᛶࡢ࠶ࡿ⠊ᅖ࡛ࠊ㐺ษ࡞ື≀ࢆ⏝࠸ࡓヨ㦂ཪࡣ &(.&,+)
࡛ࡢヨ㦂ࢆᐇ᪋ࡍࡿࡇ࡜ࠋ࡞࠾ࠊ㠀⣽⬊ᡂศཬࡧ〇㐀ᕤ⛬⏤᮶ࡢ୙⣧≀➼࡟ࡘ࠸࡚ࡣࠊ
ྍ⬟࡞㝈ࡾࠊື≀ࢆ⏝࠸ࡓヨ㦂࡛ࡣ࡞ࡃ⌮໬Ꮫⓗศᯒἲ࡟ࡼࡾホ౯ࡍࡿࡇ࡜ࠋࡲࡓࠊ᭱
⤊〇ရ࡟࠾ࡅࡿᮍศ໬⣽⬊ࡢᏑᅾࡀ␗ᡤᛶ⤌⧊ᙧᡂࡸ⭘⒆ᙧᡂ࣭ࡀࢇ໬ࡢྍ⬟ᛶ࡞࡝Ᏻ඲ᛶୖࡢ㔜せ࡞㛵ᚰ஦࡛࠶ࡿࡀࠊྍ⬟࡞㝈ࡾࠊࢭ࣭ࣝࣂࣥࢡࡸ୰㛫〇ရẁ㝵➼࡛ࡢᚭᗏⓗ࡞ゎᯒ࡟ࡼࡾࠊΰᅾࡢྍ⬟ᛶࢆྰᐃࡍࡿ࠿ࠊ࠶ࡿ࠸ࡣࠊ┠ⓗ⣽⬊࠿ࡽᮍศ໬⣽⬊ࡢຠᯝⓗศ㞳࣭㝖ཤἲࡸ୙ά໬ἲࢆ㛤Ⓨࡋࠊά⏝ࡍࡿࡇ࡜࡟ࡼࡾࠊΰᅾࡢྍ⬟ᛶࢆ᭱ᑠ㝈࡟ࡍࡿດຊࡀồࡵࡽࢀࡿࠋࡉࡽ࡟ࠊᢞ୚⤒㊰➼ࡢ㑅ᢥࡶᏳ඲ᛶୖࡢᠱᛕࢆ᭱ᑠ㝈࡟ࡍࡿࡓࡵࡢ᭷⏝࡞᪉⟇࡛࠶ࡿྍ⬟ᛶࡀ࠶ࡿࠋ
ࣄࢺ⏤᮶ࡢ〇ရࢆᐇ㦂ື≀➼࡛ヨ㦂ࡋ࡚ᚲࡎࡋࡶព⩏࠶ࡿ⤖ᯝࡀᚓࡽࢀࡿ࡜ࡣ㝈ࡽ࡞࠸ࠋࡇࡢࡓࡵࠊື≀⏤᮶ࡢ〇ရࣔࢹࣝࢆసᡂࡋ㐺ษ࡞ᐇ㦂ື≀࡟㐺⏝ࡍࡿヨ㦂⣔࡟ࡼࡾヨ㦂ࢆ⾜࠺ࡇ࡜࡛ࠊࡼࡾ᭷⏝࡞▱ぢࡀᚓࡽࢀࡿ࡜⪃࠼ࡽࢀࡿሙྜ࡟ࡣࠊࡴࡋࢁࠊࡇࡢ
ࡼ࠺࡞ヨ㦂⣔ࢆ⏝࠸ࡿࡇ࡜࡟⛉Ꮫⓗྜ⌮ᛶࡀ࠶ࡿྍ⬟ᛶࡀ࠶ࡿࠋࡑࡢ㝿ࡣࠊᑐ㇟⑌ᝈࡈ
࡜࡟㐺ษ࡞ࣔࢹࣝື≀ࢆ⏝࠸ࡓヨ㦂ࡢᐇ᪋ࢆ⪃៖ࡍࡿ㸦ὀ㸸౛࠼ࡤ⚄⤒⑌ᝈ࡞ࡽࡤࢧࣝ
➼ࠊᚠ⎔ჾ⑌ᝈ࡞ࡽࡤࣈࢱ࣭࢖ࢾ➼ࡀ㐺ࡋ࡚࠸ࡿሙྜࡀ࠶ࡿ㸧ࠋࡓࡔࡋࠊࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࢆᵓᡂࡍࡿ⣽⬊࡜ྠ୍ࡢ≉ᚩࢆ᭷ࡍࡿ⣽⬊㞟ᅋࡀྠ୍ࡢᡭἲ࡟࡚ࣄ 
㸫㸫

ࢺ௨እࡢື≀✀࠿ࡽࡶᚓࡽࢀࡿ࡜ࡣ㝈ࡽࡎࠊࡲࡓྠᵝࡢᇵ㣴᮲௳➼࡛ྠ➼㸭ྠ㉁࡞〇ရ
ࡀ〇㐀࡛ࡁࡿ࡜ࡶ㝈ࡽ࡞࠸ࡇ࡜࠿ࡽࠊࡇࡢࡼ࠺࡞ヨ㦂ࡢ᥇⏝ࠊᐇ᪋ཬࡧホ౯࡟࠶ࡓࡗ࡚
ࡣࠊៅ㔜࡞஦๓᳨ウࡸᑐᛂࡀᚲせ࡛࠶ࡿࠋࣄࢺ௨እࡢື≀✀࠿ࡽᚓࡓ & 㸦ᵝ㸧⣽⬊ຍᕤ〇ရࢆ⏝࠸࡚ື≀ᐇ㦂ࢆ⾜ࡗࡓሙྜࠊࡑࡢእᤄྍ⬟ᛶࢆㄝ᫂ࡍࡿࡇ࡜ࠋሙྜ࡟ࡼࡗ࡚
ࡣ⣽⬊ࢆ⏝࠸ࡿヨ㦂⣔ࡶ⪃៖ࡋࠊࡇࡢࡼ࠺࡞࢔ࣉ࣮ࣟࢳ࡟ࡼࡾヨ㦂ࢆ⾜࡞ࡗࡓ㝿࡟ࡣࠊࡑࡢヨ㦂⣔ࡢጇᙜᛶ࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
௨ୗ࡟ࠊᚲせ࡟ᛂࡌ࡚㠀⮫ᗋⓗ࡟Ᏻ඲ᛶࢆ☜ㄆࡍࡿ㝿ࡢཧ⪃࡟ࡍ࡭ࡁ஦㡯ཬࡧ␃ពⅬࡢ౛ࢆ♧ࡍࠋࡇࢀࡽࡣ౛♧࡛࠶ࡗ࡚ࠊྜ⌮ᛶࡢ࡞࠸ヨ㦂ࡢᐇ᪋ࢆồࡵࡿ㊃᪨࡛ࡣ࡞ࡃࠊ
〇ရࡢ≉ᛶཬࡧ⮫ᗋ㐺⏝ἲ➼ࢆ⪃៖ࡋ࡚ࠊᚲせ࠿ࡘ㐺ษ࡞ヨ㦂ࢆᐇ᪋ࡋࠊࡑࡢ⤖ᯝ࡟ࡘ࠸࡚⥲ྜⓗ࡞ほⅬ࠿ࡽホ౯ࠊ⪃ᐹࡍࡿࡇ࡜ࠋ㸯 ᇵ㣴ᮇ㛫ࢆ㉸࠼࡚ᇵ㣴ࡋࡓ⣽⬊࡟ࡘ࠸࡚ࠊ┠ⓗእࡢᙧ㉁㌿᥮ࢆ㉳ࡇࡋ࡚࠸࡞࠸ࡇ࡜
ࡸ┠ⓗ⣽⬊௨እࡢ⣽⬊ࡀ␗ᖖቑṪࡋ࡚࠸࡞࠸ࡇ࡜ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ㸰 ᚲせ࡟ᛂࡌ࡚⣽⬊࣭⤌⧊ࡀ⏘⏕ࡍࡿྛ✀ࢧ࢖ࢺ࢝࢖ࣥࠊᡂ㛗ᅉᏊ➼ࡢ⏕⌮άᛶ≀㉁ࡢᐃ㔞ࢆ⾜࠸ࠊ⏕యෆ࡬㐺⏝ࡋࡓ࡜ࡁࡢᙳ㡪࡟㛵ࡋ࡚⪃ᐹࢆ⾜࠺ࡇ࡜ࠋ
㸱 〇ရࡢ㐺⏝ࡀᝈ⪅ࡢṇᖖ࡞⣽⬊ཪࡣ⤌⧊࡟ᙳ㡪ࢆ୚࠼ࡿྍ⬟ᛶࠊཬࡧࡑࡢᏳ඲ᛶ࡟
ࡘ࠸᳨࡚ウࠊ⪃ᐹࡍࡿࡇ࡜ࠋ㸲 ᝈ⪅࡬ࡢ㐺⏝࡟ࡼࡾࠊ〇ရ୰ࡢ⣽⬊ࡸΰධࡍࡿᮍศ໬⣽⬊ࡀ␗ᡤᛶ⤌⧊ࢆᙧᡂࡍࡿ
ྍ⬟ᛶࠊཬࡧࡑࡢᏳ඲ᛶ࡟ࡘ࠸᳨࡚ウࠊ⪃ᐹࡍࡿࡇ࡜ࠋࡑࡢ㝿ࠊ〇ရࡢ✀㢮ࡸ≉ᛶࠊᢞ୚⤒㊰ࠊᑐ㇟⑌ᝈࠊཬࡧヨ㦂⣔ࡢጇᙜᛶ➼ࢆ⥲ྜⓗ࡟຺᱌ࡍࡿࡇ࡜ࠋ
㸳 〇ရཬࡧᑟධ㑇ఏᏊࡢⓎ⌧⏘≀➼࡟ࡼࡿᮃࡲࡋࡃ࡞࠸ච␿཯ᛂࡀ⏕ࡌࡿྍ⬟ᛶࠊཬࡧࡑࡢᏳ඲ᛶ࡟ࡘ࠸᳨࡚ウࠊ⪃ᐹࡍࡿࡇ࡜ࠋ㸴 ᭱⤊〇ရࡢ⣽⬊ཪࡣ୰㛫〇ရࡢ⣽⬊࡟ࡘ࠸࡚ࠊ㐺ษ࡞ື≀ࣔࢹࣝ➼ࢆ฼⏝ࡋࠊⰋᛶ⭘⒆ࢆྵࡴ⭘⒆ᙧᡂཬࡧࡀࢇ໬ࡢྍ⬟ᛶ࡟㛵ࡋ᳨࡚ウࠊ⪃ᐹࡍࡿࡇ࡜ࠋࡑࡢ㝿ࠊ〇ရࡢ✀㢮ࡸ≉ᛶࠊᢞ୚㔞࣭ᢞ୚⤒㊰ࠊ⏕╔㒊఩ࠊᑐ㇟⑌ᝈཬࡧヨ㦂⣔ࡢጇᙜᛶ➼ࢆ⥲ྜⓗ࡟຺᱌ࡍࡿࡇ࡜ࠋࡲࡓࠊ⭘⒆ᙧᡂཪࡣࡀࢇ໬ࡢྍ⬟ᛶࡀ࠶ࡿሙྜ࡟ࡣࠊᮇᚅࡉࢀࡿ
᭷ຠᛶ࡜ࡢ㛵ಀ➼ࢆ຺᱌ࡋ࡚ࠊ౑⏝ࡍࡿࡇ࡜ࡢጇᙜᛶཬࡧྜ⌮ᛶ࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍ
ࡿࡇ࡜ࠋ㸦ὀ㸸㐀⭘⒆ᛶヨ㦂࡟࠾࠸࡚᭱ࡶ㔜せ࡞ࡢࡣࠊ᭱⤊〇ရࡀᝈ⪅࡟㐺⏝ࡉࢀࡓሙྜࡢ〇ရࡢ㐀⭘⒆ᛶࢆྍ⬟࡞㝈ࡾⓗ☜࡟ホ౯ࡍࡿࡇ࡜࡛࠶ࡿࠋࡋ࠿ࡋࠊ༑ศ࡞⣽⬊ᩘࡀᚓࡽࢀ࡞࠸➼ࡢ⌮⏤࡟ࡼࡾ᭱⤊〇ရࢆᵓᡂࡍࡿ⣽⬊ࢆ⏝࠸ࡿࡇ࡜ࡀ࡛ࡁࡎࠊ୰㛫〇ရࡢ⣽⬊ࢆ⏝࠸࡚᭱⤊〇ရࡢ㐀⭘⒆ᛶࢆホ౯ࡋ࡞ࡅࢀࡤ࡞ࡽ࡞࠸ሙྜࡶ᝿ᐃࡉࢀ
ࡿࠋࡲࡓࠊື≀ࣔࢹࣝࢆ౑⏝ࡋࡓ㐀⭘⒆ᛶヨ㦂࡟࠾࠸࡚ࡣࠊ⣽⬊ࡢศᩓࡸ㊊ሙ࡬ࡢ᥋╔ࠊ⣽⬊ᐦᗘࠊᢞ୚㒊఩➼ࡢ᮲௳ࡀ᭱⤊〇ရ࡜ᚲࡎࡋࡶ୍⮴ࡍࡿࡶࡢ࡛ࡣ࡞࠸ࠋࡉࡽ
࡟ࠊື≀ࡢ✀࣭⣔⤫࣭ච␿≧ែ࡟ࡼࡿឤᗘᕪࡶ࠶ࡿࠋࡇࢀࡽࡢ஦᝟ࢆ⥲ྜⓗ࡟຺᱌ࡋ࡚ࠊ᭱⤊〇ရࡢ㐀⭘⒆ᛶࢆホ౯ࡍࡿᚲせࡀ࠶ࡿࠋࡲࡓࠊ᭱⤊〇ရࡢ㐀⭘⒆ᛶ࡟㉳ᅉࡍࡿᝈ⪅࡬ࡢࣜࢫࢡ࡟ࡘ࠸࡚ࡣࠊᑐ㇟⑌ᝈࢆ἞⒪ࡍࡿࡇ࡜࡟ࡼࡿᝈ⪅࡬ࡢ࣋ࢿࣇ࢕ࢵࢺ
➼࡜ࡢࣂࣛࣥࢫࢆ㋃ࡲ࠼࡚ྜ⌮ⓗ࡟ホ౯ࡍࡿࡇ࡜㸧ࠋ㸵 〇㐀ᕤ⛬࡛እ᮶㑇ఏᏊࡢᑟධࡀ⾜ࢃࢀࠊ᭱᪂ࡢ▱ぢ࡟ᇶ࡙ࡁࠊ᭱⤊〇ရ୰࡛ᶵ⬟ࡋ࡚࠸ࡿሙྜࡸṧᏑࡋ࡚࠸ࡿ࡜ุ᩿ࡉࢀࡓሙྜ࡟ࡣࠊ㑇ఏᏊ἞⒪⏝་⸆ရᣦ㔪࡟ᐃࡵࡿ࡜ࡇࢁ࡟‽ࡌ࡚ヨ㦂ࢆ⾜࠺ࡇ࡜ࠋ࢘࢖ࣝࢫ࣋ࢡࢱ࣮ࢆ౑⏝ࡋࡓሙྜ࡟ࡣቑṪᛶ࢘࢖ࣝࢫࡀ࡝ࡢ⛬ᗘᏑᅾࡍࡿ࠿ࢆ᳨ᰝࡍࡿ࡜࡜ࡶ࡟ࠊ᳨ᰝ᪉ἲࡀ㐺ษ࡛࠶ࡿࡇ࡜࡟ࡘ࠸࡚ࡶ 
㸫㸫

᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋ
ࡲࡓࠊᑟධ㑇ఏᏊཬࡧࡑࡢ⏘≀ࡢᛶ≧࡟ࡘ࠸࡚ㄪᰝࡋࠊᏳ඲ᛶ࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍ
ࡿࡇ࡜ࠋ⣽⬊࡟ࡘ࠸࡚ࡣࠊቑṪᛶࡢኚ໬ࠊⰋᛶ⭘⒆ࢆྵࡴ⭘⒆ᙧᡂཬࡧࡀࢇ໬ࡢྍ⬟ᛶ࡟ࡘ࠸࡚⪃ᐹࡋࠊ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠋᰁⰍయ࡬ࡢᤄධࡢྍ⬟ᛶࡀ࠶ࡿ࣋ࢡࢱ࣮ࢆ⏝࠸ࡓሙྜ࡟ࡣࠊᤄධኚ␗࡟ࡼࡿ⣽⬊ࡢ␗ᖖቑṪᛶࡸ㐀⭘⒆ᛶ࡟ࡘ࠸࡚ࡢホ౯ࡸ⮫ᗋ㐺ᛂ࡟ᙜࡓࡗ࡚ࡢ㛗ᮇࣇ࢛࣮ࣟ࢔ࢵࣉࡢᚲせᛶࢆ⪃៖ࡍࡿࡇ࡜ࠋ㸶 ື≀⏤᮶ࡢࣔࢹࣝ〇ရࢆྵࡵ࡚〇ရࡢධᡭࡀᐜ࡛᫆࠶ࡾࠊ࠿ࡘ⮫ᗋୖࡢ㐺⏝࡟㛵㐃ࡍࡿ᭷⏝࡞Ᏻ඲ᛶ᝟ሗࡀᚓࡽࢀࡿྍ⬟ᛶࡀ࠶ࡿሙྜ࡟ࡣࠊྜ⌮ⓗ࡟タィࡉࢀࡓ୍⯡ẘᛶヨ㦂ࡢᐇ᪋ࢆ⪃៖ࡍࡿࡇ࡜ࠋ
࡞࠾ࠊ୍⯡ẘᛶヨ㦂ࡢᐇ᪋࡟ᙜࡓࡗ࡚ࡣࠊᖹᡂඖᖺ  ᭶  ᪥௜ࡅ⸆ᑂ  ➨  ྕཌ⏕┬⸆ົᒁ᪂་⸆ရㄢ㛗࣭ᑂᰝㄢ㛗㐃ྡ㏻▱ࠕ་⸆ရࡢ〇㐀㍺ධᢎㄆ⏦ㄳ࡟ᚲせ࡞ẘᛶヨ㦂ࡢ࢞࢖ࢻࣛ࢖ࣥ࡟ࡘ࠸࡚ࠖࡢูῧࠕ་⸆ရẘᛶヨ㦂ἲ࢞࢖ࢻࣛ࢖ࣥࠖ➼ࢆཧ↷ࡍࡿࡇ࡜ࠋ
➨㸳❶ ࣄࢺ 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢຠຊཪࡣᛶ⬟ࢆ⿬௜ࡅࡿヨ㦂㸯 ᢏ⾡ⓗ࡟ྍ⬟࠿ࡘ⛉Ꮫⓗ࡟ྜ⌮ᛶࡢ࠶ࡿ⠊ᅖ࡛ࠊᐇ㦂ື≀ཪࡣ⣽⬊➼ࢆ⏝࠸ࠊ㐺ษ࡟タィࡉࢀࡓヨ㦂࡟ࡼࡾࠊࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢᶵ⬟Ⓨ⌧ࠊస⏝ᣢ⥆ᛶཬࡧ་⸆ရ࣭་⒪ᶵჾ࡜ࡋ࡚ᮇᚅࡉࢀࡿ⮫ᗋຠᯝࡢᐇ⌧ྍ⬟ᛶ+))%)%)(#$*,
ࢆ♧ࡍࡇ࡜ࠋ㸰 㑇ఏᏊᑟධ⣽⬊࡟࠶ࡗ࡚ࡣࠊᑟධ㑇ఏᏊ࠿ࡽࡢ┠ⓗ⏘≀ࡢⓎ⌧ຠ⋡ཬࡧⓎ⌧ࡢᣢ⥆ᛶࠊᑟධ㑇ఏᏊࡢⓎ⌧⏘≀ࡢ⏕≀άᛶ୪ࡧ࡟་⸆ရ➼࡜ࡋ࡚ᮇᚅࡉࢀࡿ⮫ᗋຠᯝࡢᐇ
⌧ྍ⬟ᛶ+))%)%)(#$*,ࢆ♧ࡍࡇ࡜ࠋ㸱 㐺ᙜ࡞ື≀⏤᮶⣽⬊࣭⤌⧊〇ရࣔࢹࣝཪࡣ⑌ᝈࣔࢹࣝື≀ࡀ࠶ࡿሙྜ࡟ࡣࠊࡑࢀࢆ
⏝࠸࡚἞⒪ຠᯝࢆ᳨ウࡍࡿࡇ࡜ࠋ㸲 ἞㦂㛤ጞẁ㝵࡛ࡣࠊᙜヱ〇ရࡢຠຊཪࡣᛶ⬟࡟ࡼࡿ἞⒪ࡀ௚ࡢ἞⒪ἲ࡜ẚ㍑ࡋࡓ࡜
ࡁࡣࡿ࠿࡟ඃࢀ࡚ᮇᚅ࡛ࡁࡿࡇ࡜ࡀᅜෆእࡢᩥ⊩ཪࡣ▱ぢ➼࡟ࡼࡾྜ⌮ⓗ࡟᫂ࡽ࠿࡟ࡉࢀ࡚࠸ࡿሙྜ࡟ࡣࠊᚲࡎࡋࡶヲ⣽࡞ᐇ㦂ⓗ᳨ウࡣᚲせ࡜ࡉࢀ࡞࠸ࠋ
➨㸴❶ ࣄࢺ 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢయෆືែ
㸯 〇ရࢆᵓᡂࡍࡿ⣽⬊࣭⤌⧊ཬࡧᑟධ㑇ఏᏊࡢⓎ⌧⏘≀࡟ࡘ࠸࡚ࠊᢏ⾡ⓗ࡟ྍ⬟࡛ࠊ࠿ࡘࠊ⛉Ꮫⓗྜ⌮ᛶࡀ࠶ࡿ⠊ᅖ࡛ࠊᐇ㦂ື≀࡛ࡢ྾཰ཬࡧศᕸ➼ࡢయෆືែ࡟㛵ࡍࡿ
ヨ㦂➼࡟ࡼࡾࠊᝈ⪅➼࡟㐺⏝ࡉࢀࡓ〇ရ୰ࡢ⣽⬊࣭⤌⧊ࡢ⏕Ꮡᮇ㛫ࠊຠᯝᣢ⥆ᮇ㛫ࢆ᥎ ࡋࠊ┠ⓗ࡜ࡍࡿຠᯝࡀ༑ศᚓࡽࢀࡿࡇ࡜ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜㸦ὀ㸸యෆືែ࡟㛵ࡍࡿヨ㦂➼࡟ࡣࠊ౛࠼ࡤ⤌⧊Ꮫⓗ᳨ウࠊ'- ἲࠊ☢Ẽඹ㬆⏬ീデ᩿ἲࠊ㝧㟁Ꮚᨺᑕ᩿ᒙ᧜ᙳἲ!ࠊ༢୍ගᏊᨺᑕ᩿ᒙ᧜ᙳἲ !ࠊࣂ࢖࢜࢖࣓࣮ࢪࣥࢢ࡞࡝
ࡀ࠶ࡿ㸧ࠋ㸰 ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢ⏝ἲ㸦ᢞ୚᪉ἲ㸧࡟ࡘ࠸࡚ࠊື≀ᐇ㦂ࢆ㏻ࡋ࡚
ࡑࡢྜ⌮ᛶࢆ᫂ࡽ࠿࡜ࡍࡿࡇ࡜ࠋ≉࡟ࠊ඲㌟ᢞ୚࡟࠶ࡗ࡚ࡣᢞ୚ᚋࡢ⣽⬊ࡢ඲㌟ศᕸࢆື≀ᐇ㦂࡞࡝࠿ࡽእᤄࡋࠊ᭷⏝ᛶࡢほⅬ࠿ࡽ㆟ㄽࡍࡿࡇ࡜㸦ὀᢞ୚⤒㊰ࡈ࡜࡟࡝ࡇ࡟⏕╔ࡍࡿ࠿ࡣ୙࡛᫂࠶ࡿࡀࠊ඲㌟ᢞ୚ࡼࡾࡶᒁᡤᢞ୚ࡀᮃࡲࡋ࠸࡜᝿ᐃࡉࢀࡿࠋ
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ࡋ࠿ࡋࠊ඲㌟ᢞ୚࡛࠶ࡗ࡚ࡶࡑࡢ᭷⏝ᛶ࡟࠾࠸࡚⿕ᢞ୚ᝈ⪅࡟᭷┈࡛࠶ࡿ࡜ྜ⌮ⓗ࡟ㄝ᫂ࡀྍ⬟࡛࠶ࡿሙྜ࡟ࡣ⏝ἲ࡜ࡋ࡚タᐃྍ⬟࡛࠶ࡿࠋ౛࠼ࡤࠊ⏕╔ࢆᮇᚅࡍࡿ⮚ჾ௨እ࡬ࡢศᕸࢆ᭱ప㝈࡟ᢚ࠼ࡿࡇ࡜ࡀྜ⌮ⓗ࡞ᢞ୚᪉ἲ࡛࠶ࡿ࡜᝿ᐃࡉࢀࡿࠋࡲࡓࠊ
␗ᡤᛶ⏕╔ࡋ࡚ࡶࠊ⿕ᢞ୚ᝈ⪅࡟࡜ࡗ࡚୙฼┈㸦⏕యᶵ⬟࡬ࡢᝏᙳ㡪㸧ࡀ⏕ࡌ࡞࠸ሙྜࡣ⏝ἲ࡜ࡋ࡚⫯ᐃ࡛ࡁࡿྍ⬟ᛶࡀ࠶ࡿࠋ␗ᡤᛶศ໬࡟ࡼࡿ୙฼┈࡜ࡣࠊ౛࠼ࡤᙜヱ⣽⬊ࡀᚰ⮚࡟␗ᡤᛶ⏕╔ࡋ࡚㦵ᙧᡂࡍࡿሙྜࡀ᝿ᐃࡉࢀࠊࡑࢀࡀ୙ᩚ⬦ࢆច㉳ࡋࡓࡼ࠺࡞ሙྜ࡛࠶ࡿ㸧ࠋ㸱 ᙜヱ⣽⬊࣭⤌⧊ࡀ≉ᐃࡢ㒊఩⤌⧊➼࡟┤᥋㐺⏝ཪࡣ฿㐩ࡋ࡚స⏝ࡍࡿሙྜ࡟ࡣࠊ
ࡑࡢᒁᅾᛶࢆ᫂ࡽ࠿࡟ࡋࠊᒁᅾᛶࡀ〇ရࡢ᭷ຠᛶ࣭Ᏻ඲ᛶ࡟ཬࡰࡍᙳ㡪ࢆ⪃ᐹࡍࡿࡇ࡜ࠋ➨㸵❶ ⮫ᗋヨ㦂ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢ⮫ᗋヨ㦂ࢆ㛤ጞࡍࡿ࡟ᙜࡓࡗ࡚ᨭ㞀࡜࡞ࡿရ㉁ཬ
ࡧᏳ඲ᛶୖࡢၥ㢟ࡀᏑᅾࡍࡿ࠿ྰ࠿ࡢẁ㝵࡟࠾ࡅࡿᏳ඲ᛶ࡟ࡘ࠸࡚ࡣࠊ⮫ᗋୖࡢ᭷⏝ᛶࢆ຺᱌ࡋ࡚ホ౯ࡉࢀࡿࡶࡢ࡛࠶ࡾࠊࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼࡟ࡘ࠸࡚ணᐃࡉࢀ
࡚࠸ࡿᅜෆࡢ⮫ᗋヨ㦂ィ⏬࡟ࡘ࠸࡚௨ୗࡢ㡯┠ࢆ㋃ࡲ࠼࡚ホ౯ࡍࡿࡇ࡜ࠋࡑࡢ㝿ࠊ᫂ࡽ࠿࡟᝿ᐃࡉࢀࡿ〇ရࡢࣜࢫࢡࢆ⌧ᅾࡢᏛၥ࣭ᢏ⾡ࢆ㥑౑ࡋ࡚᤼㝖ࡋࠊࡑࡢ⛉Ꮫⓗጇᙜᛶࢆ᫂ࡽ࠿࡟ࡋࡓୖ࡛ࠊ࡞࠾ṧࡿࠕᮍ▱ࡢࣜࢫࢡࠖ࡜ࠊ㔜⠜࡛⏕࿨ࢆ⬣࠿ࡍ⑌ᝈࠊ㌟యࡢ
ᶵ⬟ࢆⴭࡋࡃᦆ࡞࠺⑌ᝈࠊ㌟యࡢᶵ⬟ࡸᙧែࢆ୍ᐃ⛬ᗘᦆ࡞࠺ࡇ࡜࡟ࡼࡾ  ࢆⴭࡋࡃᦆ࡞࠺⑌ᝈ࡞࡝࡟⨯ᝈࡋࠊᚑ᮶ࡢ἞⒪ἲ࡛ࡣ㝈⏺ࡀ࠶ࡾࠊඞ᭹࡛ࡁ࡞࠸ᝈ⪅ࡀࠕ᪂ࡓ࡞
἞⒪ᶵ఍ࢆኻ࠺ࡇ࡜࡟ࡼࡾ⿕ࡿ࠿ࡶࡋࢀ࡞࠸ࣜࢫࢡࠖ࡜ࡢࣜࢫࢡࡢ኱ᑠࢆ຺᱌ࡋࠊ࠿ࡘࠊ
ࡇࢀࡽࡍ࡭࡚ࡢ᝟ሗࢆ㛤♧ࡋࡓୖ࡛ᝈ⪅ࡢ⮬ᕫỴᐃᶒ࡟ጤࡡࡿ࡜࠸࠺どⅬࢆᣢࡘࡇ࡜ࠊ
ࡍ࡞ࢃࡕࠊࣜࢫࢡ࣭ᮇᚅࡉࢀࡿ࣋ࢿࣇ࢕ࢵࢺࡢ᝟ሗࢆ㛤♧ࡋࡓୖ࡛἞㦂࡟ධࡿ࠿࡝࠺࠿
ࡢពᛮỴᐃࡣᝈ⪅ࡀ⾜࠺࡜࠸࠺どⅬࢆධࢀ࡚ホ౯ࡍࡿࡇ࡜ࡀᮃࡲࢀࡿࠋ㸯 ᑐ㇟⑌ᝈ㸰 ᑐ㇟࡜ࡍࡿ⿕㦂⪅ཬࡧ㝖እࡍ࡭ࡁ⿕㦂⪅ࡢ⪃࠼᪉㸱 ࣄࢺ & 㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ཬࡧే⏝⸆ࡢ㐺⏝ࢆྵࡵࡓࠊ⿕㦂⪅࡟ᑐࡋ࡚⾜ࢃࢀࡿ἞⒪ෆᐜ㸦ὀ㸸ᢞ୚࣭⛣᳜ࡋࡓ⣽⬊ࡢᶵ⬟ࢆ⥔ᣢ࣭ྥୖ࣭Ⓨ᥹ࡉࡏࡿࡓࡵ࡟ే⏝ࡍࡿ⸆๣ࡀ᝿ᐃࡉࢀࡿሙྜࠊᙜヱ⸆๣ࡢస⏝ࢆ &(.&,+) ࠶ࡿ࠸ࡣ &(.&.) ᳨࡛ドࡍࡿࡇ࡜㸧ࠋ㸲 ᪤Ꮡࡢ἞⒪ἲ࡜ࡢẚ㍑ࢆ㋃ࡲ࠼ࡓ⮫ᗋヨ㦂ᐇ᪋ࡢጇᙜᛶ㸳 ⌧ᅾᚓࡽࢀ࡚࠸ࡿ᝟ሗ࠿ࡽ᝿ᐃࡉࢀࡿ〇ရ୪ࡧ࡟ᝈ⪅ࡢࣜࢫࢡཬࡧ࣋ࢿࣇ࢕ࢵࢺ
ࢆྵࡵࠊ⿕㦂⪅࡬ࡢㄝ᫂஦㡯ࡢ᱌࡞࠾ࠊ⮫ᗋヨ㦂ࡣࠊ㐺ษ࡞ヨ㦂ࢹࢨ࢖ࣥཬࡧ࢚ࣥࢻ࣏࢖ࣥࢺࢆタᐃࡋ࡚ᐇ᪋ࡍࡿᚲ
せࡀ࠶ࡾࠊ┠ⓗ࡜ࡍࡿ⣽⬊࣭⤌⧊ࡢ⏤᮶ࠊᑐ㇟⑌ᝈཬࡧ㐺⏝᪉ἲ➼ࢆ㋃ࡲ࠼࡚㐺ษ࡟ィ⏬ࡍࡿࡇ࡜ࠋ
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㸫㸫⸆⏕⸆ᑂⓎ  ➨㸯ྕ⸆⏕ᶵᑂⓎ  ➨㸯ྕ௧࿴ඖᖺ㸳᭶㸶᪥ ྛ㒔㐨ᗓ┴⾨⏕୺⟶㒊㸦ᒁ㸧㛗 Ẋཌ⏕ປാ┬་⸆࣭⏕ά⾨⏕ᒁ་⸆ရᑂᰝ⟶⌮ㄢ㛗 㸦 බ ༳ ┬ ␎ 㸧ཌ⏕ປാ┬་⸆࣭⏕ά⾨⏕ᒁ་⒪ᶵჾᑂᰝ⟶⌮ㄢ㛗㸦 බ ༳ ┬ ␎ 㸧ᛴᛶᮇ⬨㧊ᦆയࡢ἞⒪ࢆ┠ⓗ࡜ࡋࡓ་⸆ရ➼ࡢ⮫ᗋホ౯࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥ࡟ࡘ࠸࡚
ᛴᛶᮇ⬨㧊ᦆയ἞⒪ࢆ┠ⓗ࡜ࡋࡓ་⸆ရ➼ࡢ〇㐀㈍኎ࡢᢎㄆ⏦ㄳࡢࡓࡵ࡟ᐇ᪋ࡉࢀࡿࠊ
⮫ᗋヨ㦂ࡢホ౯᪉ἲ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࢆࠊู⣬ࡢ࡜࠾ࡾసᡂࡋࡲࡋࡓࡢ࡛ࠊ㈗⟶ୗ㛵ಀᴗ⪅➼࡟ᑐࡋ࿘▱᪉ᚚ㓄៖㢪࠸ࡲࡍࠋᮏ࢞࢖ࢻࣛ࢖ࣥࡣࠊ୺࡟་⸆ရࡢ⮫ᗋホ౯࡟ά⏝ࡍࡿࡓࡵ࡟సᡂࡋࡓࡶࡢ࡛ࡍࡀࠊᮏ࢞࢖ࢻࣛ࢖ࣥ࡟♧ࡍ⪃࠼᪉ࡣ෌⏕་⒪➼〇ရࡢ⮫ᗋホ౯ࢆ⾜࠺㝿࡟ࡶ᭷⏝࡛࠶ࡿࡓࡵࠊཧ⪃࡜ࡋ࡚ࡃࡔࡉ࠸ࠋ࡞࠾ࠊᮏ࢞࢖ࢻࣛ࢖ࣥࡣࠊ⌧᫬Ⅼ࡟࠾ࡅࡿ⛉Ꮫⓗ▱ぢ࡟ᇶ࡙ࡃᇶᮏⓗ⪃࠼᪉ࢆࡲ࡜ࡵࡓࡶࡢ࡛࠶ࡾࠊᏛၥୖࡢ㐍Ṍ➼ࢆ཯ᫎࡋࡓྜ
⌮ⓗ᰿ᣐ࡟ᇶ࡙࠸ࡓࡶࡢ࡛࠶ࢀࡤࠊᚲࡎࡋࡶࡇࡇ࡟♧ࡋࡓ᪉ἲࢆᅛᏲࡍࡿࡼ࠺ồࡵࡿࡶࡢ࡛ࡣ࠶ࡾࡲࡏࢇࠋ㸫㸫

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ᛴᛶᮇ⬨㧊ᦆയࡢ἞⒪ࢆ┠ⓗ࡜ࡋࡓ་⸆ရ➼ࡢ⮫ᗋホ౯࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥ┠ḟ ⥴ゝ...............................................................................................................................................3 ␿Ꮫ........................................................................................................................................3 ⑓ែ........................................................................................................................................3 ᮏ࢞࢖ࢻࣛ࢖ࣥࡢ఩⨨௜ࡅ................................................................................................4 ⮫ᗋホ౯᪉ἲ...............................................................................................................................4 ᑐ㇟㞟ᅋ................................................................................................................................5 ⤌ධࢀ࡟࠾ࡅࡿ㑅ᢥᇶ‽.............................................................................................5 ⤌ධࢀ࡟࠾ࡅࡿ㝖እᇶ‽.............................................................................................6 㧗㱋⪅࡟ࡘ࠸࡚.............................................................................................................6 ⑕౛ᩘࡢタᐃ........................................................................................................................6 ᭷ຠᛶホ౯............................................................................................................................6 ୺せホ౯㡯┠.................................................................................................................7 ๪ḟホ౯㡯┠.................................................................................................................7 Ᏻ඲ᛶホ౯............................................................................................................................8 ే⏝⚗Ṇ⸆ཬࡧే⏝⚗Ṇ⒪ἲࡢタᐃ................................................................................9 ే⏝⚗Ṇ⸆.....................................................................................................................9 ే⏝⚗Ṇ⒪ἲ.................................................................................................................9 ࡑࡢ௚ࡢ␃ព஦㡯................................................................................................................9 ヨ㦂ᐇ᪋యไ.................................................................................................................9 ⿕㦂⪅⫼ᬒࡢグ㘓...........................................................................................................9 ⮫ᗋヨ㦂.....................................................................................................................................10 ⮫ᗋ⸆⌮ヨ㦂......................................................................................................................10 ┠ⓗ...............................................................................................................................10 ヨ㦂ィ⏬࡟㛵ࡍࡿ␃ពⅬ...........................................................................................10 ࡑࡢ௚ࡢ␃ព஦㡯.......................................................................................................11 ᥈⣴ⓗヨ㦂..........................................................................................................................11 ┠ⓗ...............................................................................................................................11 ヨ㦂ィ⏬࡟㛵ࡍࡿ␃ពⅬ...........................................................................................11 ᳨ドⓗヨ㦂..........................................................................................................................11㸫㸫

 ┠ⓗ...............................................................................................................................11 ヨ㦂ィ⏬࡟㛵ࡍࡿ␃ពⅬ...........................................................................................12
 〇㐀㈍኎ᚋㄪᰝ➼.....................................................................................................................12 ⏝ㄒ࣭␎ㄒ.................................................................................................................................12 ཧ⪃㈨ᩱ.....................................................................................................................................13
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㸫㸫 ⥴ゝ⬨㧊ᦆയࡣ඲ୡ⏺࡛ᬑ㐢ⓗ࡟ࡳࡽࢀࠊ἞⒪࡟ࡼࡗ࡚ࡶ༑ศᨵၿࡀᚓࡽࢀࡎࠊ㛗ᮇ࡟ࢃࡓࡾ
ᝈ⪅ࡢࡳ࡞ࡽࡎᐙ᪘࡟ᑐࡍࡿ⢭⚄ⓗཬࡧ♫఍ⓗ࡞㈇ᢸ୪ࡧ࡟⤒῭ⓗᦆኻࡣ኱ࡁࡃࠊࡑࡢᑐฎࡣ㔜せ࡛࠶ࡿࠋ
ᛴᛶᮇ⬨㧊ᦆയࡢ἞⒪ࢆ┠ⓗ࡜ࡋࡓ་⸆ရ➼ࡢ⮫ᗋホ౯ࡢ᪉ἲ࡟ࡘ࠸࡚ࡣࠊ༓ⴥ኱Ꮫ኱
Ꮫ㝔་Ꮫ◊✲㝔ࡀࠊཌ⏕ປാ┬㠉᪂ⓗ་⸆ရ࣭་⒪ᶵჾ࣭෌⏕་⒪➼〇ရᐇ⏝໬ಁ㐍஦ᴗ෌⏕་⒪➼〇ရ㸦⬨㧊ᦆയ࣭⚄⤒෌⏕㸧ࡢ⮫ᗋᛂ⏝࡟࠾࠸࡚ࠕᛴᛶᮇ⬨㧊ᦆയ࡟࠾ࡅࡿ⮫ᗋホ౯࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥ㸦᱌㸧ࠖࢆసᡂࡋሗ࿌ࡋࡓࠋ
௒⯡ࠊ๓ฟࡢ࢞࢖ࢻࣛ࢖ࣥ᱌ࢆᇶ࡟ࠊ༓ⴥ኱Ꮫ኱Ꮫ㝔་Ꮫ◊✲㝔࡜⊂❧⾜ᨻἲே་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ࡜ࡢ༠ຊࡢୗࠊࡉࡽ࡟᳨ウࢆ⾜࠸ࠊᛴᛶᮇ⬨㧊ᦆയࡢ἞⒪ࢆ┠ⓗ࡜ࡋࡓ་⸆
ရ➼ࡢ㛤Ⓨ࡟࠾ࡅࡿ⮫ᗋホ౯࡟࠾࠸࡚⪃៖ࡍ࡭ࡁⅬࢆᮏ࢞࢖ࢻࣛ࢖ࣥ࡜ࡋ࡚ྲྀࡾࡲ࡜ࡵࡓࠋ
 ␿Ꮫ ᮏ㑥࡛ᖺ㛫⣙ 4,000㹼5,000 ேࡀ⬨㧊ᦆയࢆ⨯ᝈࡋ࡚࠾ࡾࠊࡑࡢ㞴἞ᛶ࡟ࡼࡾ⌧ᅾࡢᝈ⪅⥲ᩘࡣ 10㹼20 ୓ே௨ୖ࡜࠸ࢃࢀ࡚࠸ࡿ 1, 2)ࠋእയ࡟ࡼࡾ⬨㧊ࡀᦆയࡉࢀࡿ࡜ࠊᅄ⫥ࡢ㐠ື࣭ឤぬ㯞⑷ࠊ⭤⬔࣭┤⭠ᶵ⬟㞀ᐖ➼ࠊ✀ࠎࡢ⑕≧ࢆ࿊ࡍࡿࠋ⌧ᅾࡢ་Ꮫ࡛ࡣᦆയࡋࡓ⬨㧊ࡑࡢࡶࡢࢆ᚟ඖࡉࡏ㯞⑷ࢆᅇ᚟ࡉࡏࡿࡇ࡜ࡣ୙ྍ⬟࡛࠶ࡾࠊ⬨᳝ࡢ⬺⮻࣭㦵ᢡࡀ࠶ࡿሙྜࡣࠊᏳ
ᐃ໬ࡉࡏࡿᡭ⾡ཬࡧṧᏑࡋࡓᶵ⬟ࢆ᭱኱㝈࡟ά⏝ࡍࡿࡓࡵࡢࣜࣁࣅࣜࢸ࣮ࢩࣙࣥࡢࡳࡀ⾜ࢃࢀ 3, 4)ࠊ᥎ዡࡍ࡭ࡁ἞⒪ἲࡀᏑᅾࡋ࡞࠸ࡢࡀ⌧≧࡛࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊ⬨㧊ᦆയᚋࡢ㯞⑷ࡢணᚋࡣཷയ࣭⨯⑓┤ᚋࡢ⤌⧊ᦆയࡢ⛬ᗘ࡟ࡼࡾ࡯ࡰỴᐃࡉࢀ࡚ࡋࡲࡗ࡚࠸ࡿ࡜࠸࠼ࡿࠋ
 ⑓ែ ⬨㧊ᦆയࡣᦆയᚋࡢ᫬㛫⤒㐣࡜࡜ࡶ࡟ࠊᦆയ࡟ᑐࡍࡿ⏕య཯ᛂ࡟ࡼࡾ⑓ែࡀ」㞧࡟ኚ໬ࡍࡿࡓࡵࠊࡑࢀࡒࢀࡢ᫬ᮇ࡟ࡑࢀࡒࢀࡢ⑓ែ࡟༶ࡋࡓ㐺ษ࡞἞⒪ࡀᚲせ࡟࡞ࡿࠋ
 ᛴᛶᮇ㸸⬨㧊ᦆയࡢᛴᛶᮇࡣእຊ࡟ࡼࡿ୍ḟᦆയ࡜ࠊᘬࡁ⥆࠸࡚㉳ࡇࡿ⏕໬Ꮫⓗ࣭⏕≀Ꮫⓗ཯ᛂ࡛࠶ࡿ஧ḟᦆയ࡟ศ㢮ࡉࢀࡿࠋ⾑⭘ࠊ⹫⾑ࠊᾋ⭘ࠊ⅖⑕⣽⬊ᾐ₶ཬࡧ⚄⤒ఏ㐩≀㉁ࡢ₃ฟ࡟ࡼࡿ⣽⬊ẘᛶ➼࡟ࡼࡾ⚄⤒࣭ࢢࣜ࢔⣽⬊ࡢ⣽⬊Ṛࡀᘬࡁ㉳ࡇࡉࢀ㞀ᐖ⠊ᅖࡀᣑ኱ࡋ࡚࠸ࡃ㐣⛬ࢆ⥲⛠ࡋ࡚஧ḟᦆയ࡜࿧ࢇ࡛࠸ࡿࠋ஧ḟᦆയࡣ୍ḟᦆയ࡜␗࡞ࡾྛ✀἞⒪ࡢ୺ࡓࡿࢱ࣮ࢤࢵࢺ࡜࡞ࡾ࠺ࡿ⑓ែ࡛࠶ࡿ 5)ࠋࡍ࡞ࢃࡕࠊ
἞⒪࡟ࡼࡾ஧ḟᦆയࢆᢚไࡋ࡚⤌⧊㞀ᐖࢆ᭱ᑠ㝈࡟㣗࠸Ṇࡵࡿࡇ࡜࡛ࠊᶵ⬟ணᚋࢆᨵၿ࡛ࡁࡿྍ⬟ᛶࡀ࠶ࡿࠋᛴᛶᮇ࡟ࡣ᫬㛫ⓗไ⣙➼ࡢほⅬ࠿ࡽ୺࡟⸆≀⒪ἲࡀ
᳨ウࡉࢀ࡚࠸ࡿࠋ࡞࠾ࠊᾏእࡢ࢞࢖ࢻࣛ࢖࡛ࣥࡣࠊ㏻ᖖཷയᚋ 3 ᪥௨ෆ࡟ᐇ᪋ࡋ
ࡓ἞⒪ࢆᛴᛶᮇ἞⒪࡜⪃࠼ࡿࡀࠊᛴᛶᮇࡢᮇ㛫࡟ࡘ࠸࡚ࡣ㆟ㄽࡢవᆅࡀ࠶ࡿ࡜ࡉ
ࢀ࡚࠸ࡿ 6)ࠋ
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3
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 ៏ᛶᮇ㸸⬨㧊ᦆയ㒊࡟ࡣ✵Ὕࡀᙧᡂࡉࢀ⤌⧊Ḟᦆ࡜࡞ࡿࠋᦆയ㒊࿘ᅖ࡟㞟⠵ࡋࡓ࢔ࢫࢺࣟ
ࢧ࢖ࢺࡣ◳࠸ࢢࣜ࢔⒕⑞ࢆᙧᡂࡋࠊ㍈⣴෌⏕࡟ᑐࡍࡿࣂ࣮ࣜࣖ࡜࡞ࡿࠋࡲࡓ⬨㧊ᦆയࡢ៏ᛶᮇ࡛ࡣ⚄⤒⣽⬊ࡢάᛶࡀపୗࡋࠊ⣽⬊యࡢⴎ⦰ࢆࡁࡓࡍࡇ࡜ࡀ▱ࡽࢀ࡚࠾ࡾࠊ἞⒪࡬ࡢ཯ᛂᛶࡀపୗࡋ࡚࠸ࡿྍ⬟ᛶࡀ♧၀ࡉࢀ࡚࠸ࡿࠋ
 ࡇࡢࡼ࠺࡟⬨㧊ᦆയ࡛ࡣཷയᚋࡢ᫬ᮇ࡟ࡼࡾ⑓ែࡀ኱ࡁࡃ␗࡞ࡿࡓࡵࠊᛴᛶᮇ࣭ளᛴᛶ
ᮇ࣭៏ᛶᮇ࡟ᑐࡍࡿ㐺ษ࡞⮫ᗋホ౯ࡢ᪉ἲࡣࡑࢀࡒࢀ␗࡞ࡿࠋ

 ᮏ࢞࢖ࢻࣛ࢖ࣥࡢ఩⨨௜ࡅ ᮏ࢞࢖ࢻࣛ࢖ࣥࡣࠊ୺࡟ᛴᛶᮇ⬨㧊ᦆയࡢ἞⒪ࢆ┠ⓗ࡜ࡋࡓ་⸆ရࡢ㛤Ⓨ࡟࠾࠸࡚᭷ຠ
ᛶཬࡧᏳ඲ᛶࢆ᳨ウࡍࡿࡓࡵࡢࠊ⮫ᗋヨ㦂ࡢィ⏬ࠊᐇ᪋ཬࡧホ౯ἲ➼࡟ࡘ࠸࡚ᶆ‽ⓗ᪉ἲ࡜ᡭ㡰ࢆᴫㄝࡋࡓࡶࡢ࡛࠶ࡿࠋ⬨㧊ᦆയࡢ࠺ࡕࠊளᛴᛶᮇཬࡧ៏ᛶᮇࡢ἞⒪࡟࠾ࡅࡿ་⸆ရ➼ࡢ㛤Ⓨ࡟㛵ࡋ࡚ࡣู㏵㐺ษ࡞᪉ἲ᳨࡛ウࡍࡿࡇ࡜ࠋࡲࡓࠊᮏ࢞࢖ࢻࣛ࢖࡛ࣥࡣࠊᑐ㇟࡜࡞ࡿ
⑌ᝈ㡿ᇦ࡟ࡼࡽࡎඹ㏻ࡍࡿ஦㡯ࡢグ㍕ࡣྍ⬟࡞㝈ࡾ㑊ࡅࡓࡓࡵࠊ⮫ᗋヨ㦂ᐇ᪋࡟ಀࡿ୍⯡ⓗ࡞஦㡯ࡣ㛵㐃ࡍࡿἲ௧㏻▱㸦ICH ࢞࢖ࢻࣛ࢖ࣥࢆྵࡴࠋ
㸧ࢆ㐺ᐅཧ↷ࡍࡿࡇ࡜ࠋ
୍᪉ࠊ་Ꮫࡣ௒ᚋࡶ㐍Ṍࡍࡿࡇ࡜ࡀண᝿ࡉࢀࠊ᪂ࡋ࠸▱ぢ࡟ᇶ࡙ࡁࠊᮏ࢞࢖ࢻࣛ࢖ࣥࡶ㐺ᐅᨵゞࡉࢀࡿ࡭ࡁ࡛࠶ࡿࠋࡲࡓࠊ⛉Ꮫⓗ࡟ጇᙜ࡞⌮⏤ࡀ࠶ࡿሙྜ࡟ࡣࠊᮏ࢞࢖ࢻࣛ࢖ࣥࡢෆ
ᐜ࡟ᣊࡿࡇ࡜࡞ࡃࠊᰂ㌾࡞ᑐᛂࡀᮃࡲࢀࡿࠋ ࡞࠾ࠊᮏ࢞࢖ࢻࣛ࢖ࣥ࡟♧ࡍ⪃࠼᪉ࡣࠊ෌⏕་⒪➼〇ရࡢ⮫ᗋホ౯ࢆ⾜࠺㝿࡟ࡶ᭷⏝࡛࠶ࡿࡓࡵࠊ෌⏕་⒪➼〇ရࡢ⮫ᗋホ౯࡟࠾࠸࡚ࡶᮏ࢞࢖ࢻࣛ࢖ࣥࢆཧ⪃࡟ࡉࢀࡓ࠸ࠋ ࡲࡓࠊ㠀እയᛶࡢᛴᛶᮇ⬨㧊ᦆയࡢ἞⒪ࢆ┠ⓗ࡜ࡋࡓ་⸆ရ➼ࡢ㛤Ⓨ࡟࠾࠸࡚ࡶࠊᮏ࢞࢖
ࢻࣛ࢖ࣥࡢ⪃࠼᪉ࢆཧ⪃࡟࡛ࡁࡿࠋ
 ⮫ᗋホ౯᪉ἲ ⬨㧊ᦆയࢆᑐ㇟࡜ࡋࡓ⮫ᗋヨ㦂࡟㝿ࡋ࡚⪃៖ࡍ࡭ࡁ⑌ᝈࡢ≉ᚩ࡜ࡋ࡚ࠊձ⮬↛ᅇ᚟ࡀᑡ࡞ࡃ࡞࠸ 6, 7)ࠊղཷയᚋ᪩ᮇ࡛ࡣ⑕≧ࡀᏳᐃࡋ࡚࠸࡞࠸ࠊճཷയ᫬ࡢ㔜⑕ᗘཬࡧᦆയ㧗఩࡟ࡼࡾ⚄⤒⑕≧ࡀከᙬ࡛࠶ࡾࠊࡲࡓࡑࡢᨵၿ⛬ᗘࡀ␗࡞ࡿ 6, 7, 8)ࠊմ୍⯡ⓗ࡟⏝࠸ࡽࢀࡿࡇ࡜
ࡢከ࠸⚄⤒⑕≧ホ౯ἲ࡜᪥ᖖ⏕άືస㸦ADL㸧㸭⏕άࡢ㉁㸦QOL㸧࡜ࡢ㛵㐃ࡀ᏶඲࡟ࡣ᫂ࡽ
࠿࡟ࡉࢀ࡚࠸࡞࠸ 9)ࠊյ௓ධ᫬ᮇ࡜௓ධ᫬ࡢ㔜⑕ᗘ࡛ᮇᚅࡉࢀࡿᨵၿຠᯝࡀ␗࡞ࡿ 10)Ⅼ➼ࡀ࠶ࡿࠋ ᮏ㡯࡛ࡣࠊᛴᛶᮇ⬨㧊ᦆയࢆᑐ㇟࡜ࡋࡓ⸆≀⒪ἲ➼࡟㛵ࡍࡿ⮫ᗋヨ㦂ࡢィ⏬❧᱌࡟㛵ࡍࡿ⥲ㄽ࡜ࡋ࡚ࠊ᥈⣴ⓗヨ㦂ཬࡧ᳨ドⓗヨ㦂࡟࠾ࡅࡿ␃ពⅬ࡟ࡘ࠸࡚ㄝ᫂ࡍࡿࠋ

4㸫㸫

 ᑐ㇟㞟ᅋ ⮫ᗋヨ㦂࡟࠾࠸࡚ࡣࠊ᭷ຠᛶཬࡧᏳ඲ᛶホ౯࡟㐺ࡋࡓ㞟ᅋࢆ㑅ᢥࡍࡿࡓࡵ࡟ࠊᅜ㝿ⓗ࡟ᬑཬࡋࡓデ᩿ᇶ‽ࠊ㔜⑕ᗘศ㢮➼ࢆ⏝࠸࡚㑅ᢥᇶ‽ࢆタᐃࡍࡿᚲせࡀ࠶ࡿࠋ⬨㧊ᦆയࡣᦆയ㧗఩࣭㔜⑕ᗘ࡟ࡼࡾ⑕≧ࡀከᙬ࡛࠶ࡿࡇ࡜࠿ࡽࠊ᭷ຠᛶホ౯࡟㐺ࡋࡓ㞟ᅋࢆ⤠ࡾ㎸ࡴࡓࡵࡢ㑅ᢥᇶ‽ࡢタᐃ࡟㝿ࡋࠊ⿕㦂⸆ࡢ≉ᛶࡸヨ㦂ࡢ┠ⓗ࡟ᛂࡌ࡚ࠊ㔜⑕ᗘࡸᦆയ㧗఩ࢆ࠶ࡿ⛬ᗘ㝈ᐃࡍࡿࡇ࡜ࡀ㐺ษ࡞ሙྜࡀ࠶ࡿࠋࡋ࠿ࡋ࡞ࡀࡽࠊ⮫ᗋヨ㦂࡛㝖እࡉࢀࡓ㔜⑕ᗘࡸᦆയ㧗఩࡟ᑐࡋ࡚౑⏝ࡋࡓ㝿ࡢ᭷ຠᛶཬࡧᏳ඲ᛶ࡟ࡘ࠸࡚ࠊ⮫ᗋヨ㦂࡛ᚓࡽࢀࡓᡂ⦼ࡢ୍⯡໬ྍ⬟ᛶࡢ᳨ウࡸࠊ㏣ຍࡢ⮫ᗋヨ㦂➼࡟ࡼࡿ᝟ሗ཰㞟ࢆ᳨ウࡍࡿᚲせࡀ࠶ࡾࠊ⊂❧⾜ᨻἲே་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ࡜஦๓࡟༠㆟ࡍࡿࡇ࡜ࡀ່ࡵࡽࢀࡿࠋ
 ⤌ධࢀ࡟࠾ࡅࡿ㑅ᢥᇶ‽ ヨ㦂἞⒪ࡢ௓ධ᫬ᮇ࡟ࡘ࠸࡚ ᛴᛶᮇ⬨㧊ᦆയ࡟ᑐࡍࡿ⮫ᗋヨ㦂ࡢሙྜ࡟ࡣࠊᛴᛶᮇࡢ࡝ࡢ᫬Ⅼ࡛἞⒪௓ධࢆ⾜࠺ࡢ࠿ࢆ᳨ウࡍࡿᚲせࡀ࠶ࡿࠋཷയᚋ᪩ᮇ࡛࠶ࡿ࡯࡝⬨㧊ࢩࣙࢵࢡࡢᙳ㡪ࡶ࠶ࡾ⚄⤒⑕≧ࡀ୙Ᏻᐃ࡛࠶ࡿࡓࡵ 11)ࠊཷയ┤ᚋ㸦≉࡟ 24 ᫬㛫௨ෆ㸧࡛ࡣࠊ㯞⑷ࡢ㔜⑕ᗘࡸ⚄⤒⑕≧࡟㛵ࡋ࡚ࡢ㐺ษ࡞ホ౯ࡀ㞴ࡋࡃࠊ⤖ᯝ࡜ࡋ࡚᭷ຠᛶࡢホ౯ࡀᅔ㞴࡜࡞ࡗ࡚ࡋࡲ࠺ྍ⬟ᛶࡀ࠶ࡿ 6, 11)ࠋཷ
യࡢᩘ᪥ᚋ࡟ࡣ⚄⤒⑕≧ࡣࡸࡸᏳᐃࡍࡿ࡜ࡉࢀ࡚࠸ࡿࡓࡵ 11)ࠊ⿕㦂⪅ࡢ⚄⤒⑕≧ࢆヲ⣽࡟ホ౯࡛ࡁࡿࠋࡇࢀࡽࢆ㋃ࡲ࠼ࠊ㐺ษ࡞௓ධ᫬ᮇ࡟ࡘ࠸࡚ࡣࠊ⿕㦂⸆ࡢ≉ᛶࡸヨ㦂ࡢ┠ⓗ࡟ᛂࡌ࡚ࠊಶู࡟᳨ウࡍ࡭ࡁ࡛࠶ࡿࠋࡲࡓࠊᢞ୚ᮇ㛫ࠊ⥅⥆ᢞ୚ࡢせྰཬࡧ⥅⥆ᢞ୚ࡢሙྜࡢᢞ
⸆୰Ṇ᫬ᮇ࡟㛵ࡋ࡚ࡶࠊ⿕㦂⸆ࡢ≉ᛶࡸヨ㦂ࡢ┠ⓗ࡟ᛂࡌࡓಶูࡢ᳨ウࢆせࡍࡿࠋ ᑐ㇟ᝈ⪅ࡢᦆയ㧗఩࡟ࡘ࠸࡚
⬨㧊ᦆയ࡛ࡣཷയ᫬ࡢᦆയ㧗఩࡟ࡼࡾᨵၿࡢ⛬ᗘࡀ␗࡞ࡿ࡜ࡉࢀ࡚࠸ࡿࡓࡵࠊᛴᛶᮇ⬨㧊ᦆയࢆᑐ㇟࡜ࡋࡓヨ㦂࡛ࡣࠊ㐺ษ࡞᭷ຠᛶホ౯ࢆ⾜࠺ࡓࡵ࡟ࠊᑐ㇟ᝈ⪅ࡢᦆയ㧗఩ࢆ㝈ᐃࡍࡿࡇ࡜ࡀ᭷⏝࡛࠶ࡿ 10)ࠋ
⬚㧊ᦆയࡣ㢁㧊ᦆയ࡜ẚ㍑ࡋ࡚᏶඲㯞⑷ࡢ๭ྜࡀ㧗࠸࡜࠸࠺ᦆയ⛬ᗘࡢ㐪࠸ࡀ࠶ࡿ 12)ࠋ⬚㧊ᦆയ࡛ࡣ㯞⑷ࡢᅇ᚟࡟ࡼࡾࠊ⚄⤒Ꮫⓗᦆയ㧗఩ࡀపୗࡋ࡚ࡶ㐠ື㯞⑷࡜ࡋ࡚ࡣ୙ኚ㸦⚄⤒Ꮫⓗᦆയ㧗఩ࡢୗ㝆ࡀ ASIA 㐠ື score ➼ࡢ⚄⤒Ꮫⓗホ౯࡜┦㛵ࡋ࡞࠸ࡇ࡜ࢆ࠸࠺ࠋ
㸧࡜࡞ࡿࡇ࡜ࡀ࠶ࡾࠊASIA 㐠ື score ࡀᚲࡎࡋࡶ㯞⑷ࡢᅇ᚟ࢆ཯ᫎࡋ࡞࠸ࠋࡇࢀ࡟ᑐࡋ࡚ࠊ㢁㧊ᦆയ࡛ࡣ⚄⤒Ꮫⓗᦆയ㧗఩ࡢഹ࠿࡞ୗ㝆ࡶ㐠ື㯞⑷ࡢᨵၿ࡜ࡋ࡚㗦ᩄ࡟ᤊ࠼ࡿࡇ࡜ࡀྍ
⬟࡛࠶ࡿࠋ Ᏻ඲ᛶࡢほⅬ࠿ࡽࠊ㢁㧊ᦆയ㧗఩ࢆ㝈ᐃࡍࡿሙྜࠊ୍⯡࡟ୖ఩㢁㧊➼࡛ࡣ㔜⠜࡞࿧྾㯞⑷ࢆ⏕ࡌ࠺ࡿࡓࡵࠊ࿧྾㯞⑷ࢆ⏕ࡌࡓ⑕౛ࢆᑐ㇟㞟ᅋ࡟⤌ࡳධࢀࡿ࠿࡝࠺࠿஦๓࡟᳨ウࡍࡿ
ᚲせࡀ࠶ࡿࠋ
  ᑐ㇟ᝈ⪅ࡢ㔜⑕ᗘ࡟ࡘ࠸࡚
5㸫㸫

⬨㧊ᦆയ࡛ࡣཷയ᫬ࡢ㔜⑕ᗘ࡟ࡼࡾᨵၿࡢ⛬ᗘࡀ␗࡞ࡿྍ⬟ᛶࡀ࠶ࡿࡓࡵࠊ⮫ᗋヨ㦂࡟࠾࠸࡚㐺ษ࡞ᝈ⪅㑅ᢥࢆ⾜࠺ୖ࡛ࠊᅜ㝿ⓗ࡟ᬑཬࡋࡓ㔜⑕ᗘศ㢮ࢆ㑅ᢥᇶ‽࡜ࡋ࡚つᐃࡍࡿࡇ࡜ࡣ㔜せ࡛࠶ࡿࠋ⸆ຠホ౯ࡢほⅬ࠿ࡽࠊᝈ⪅㞟ᅋࢆ௦⾲ࡋ࡚࠾ࡾࠊ᭷ຠᛶཬࡧᏳ඲ᛶࢆ㐺ษ࡟ホ౯ྍ⬟࡞ᝈ⪅ࢆ⤌ࡳධࢀࡿᚲせࡀ࠶ࡿࠋ
 ⤌ධࢀ࡟࠾ࡅࡿ㝖እᇶ‽ 㝖እᇶ‽ࡢタᐃࡢ㝿࡟ࡣࠊ⬨㧊ᦆയࡢணᚋ࡟ᙳ㡪ࢆ୚࠼ࡿྍ⬟ᛶࡀ࠶ࡿᡭ⾡᪋⾜ࡢ᭷↓ࠊࢫࢸࣟ࢖ࢻ⒪ἲ➼ࡢᅉᏊ࡟ࡘ࠸᳨࡚ウࡍࡿࡇ࡜ࡀ㔜せ࡛࠶ࡿࠋᡭ⾡᪋⾜ࡀ⬨㧊ᦆയ࡟ࡼࡿ
㯞⑷ࡢணᚋ࡟୚࠼ࡿᙳ㡪࡟ࡘ࠸࡚ࡣࠊ᪩ᮇࡢᡭ⾡ࡀ㯞⑷ࢆᨵၿࡉࡏࡓ࡜࠸࠺ሗ࿌ 13) ࡀ࠶ࡿ୍᪉ࠊᡭ⾡ࡢ᭷↓ࡣ㯞⑷ࡢணᚋ࡜㛵ಀ࡞࠸࡜࠸࠺ሗ࿌ࡶ࠶ࡾ 14, 15)ࠊࢥࣥࢭࣥࢧࢫࡀᚓࡽࢀ
࡚࠸࡞࠸ࠋࡓࡔࡋࠊ⬺⮻࡟㛵ࡋ࡚ࡣ᪩ᮇࡢᩚ᚟ࡀⰋ࠸࡜ࡉࢀ࡚࠸ࡿ 16)ࠋᡭ⾡᪋⾜ࡀ᭷ຠᛶཬ
ࡧᏳ඲ᛶࡢホ౯࡟୚࠼ࡿᙳ㡪࡟ࡘ࠸࡚ࡣࠊ⌧᫬Ⅼ࡛ࡣ୙࡛᫂࠶ࡿࡓࡵࠊᡭ⾡᪋⾜ࡢ᭷↓ࢆ㝖እᇶ‽࡜ࡋ࡚タᐃࡍࡿ࠿࡟ࡘ࠸࡚ࡣࠊಶࠎࡢ⮫ᗋヨ㦂ࡢィ⏬ẁ㝵᳨࡛ウࡍࡿᚲせࡀ࠶ࡿࠋࡲ
ࡓࠊヨ㦂㛤ጞ๓࡟ࢫࢸࣟ࢖ࢻ⒪ἲࡀ᪋⾜ࡉࢀࡓᝈ⪅ࡢ⤌ධࢀ࡟ࡘ࠸࡚ࡶࠊ᭷ຠᛶཬࡧᏳ඲ᛶホ౯࡟ᙳ㡪ࢆ୚࠼࠺ࡿᅉᏊࡢࡦ࡜ࡘ࡜ࡋ࡚ࠊィ⏬ẁ㝵᳨࡛ウࡍࡿᚲせࡀ࠶ࡿࠋ
 㧗㱋⪅࡟ࡘ࠸࡚ ⬨㧊ᦆയࡣࠊ㧗㱋⪅㸦65 ṓ௨ୖ㸧࡛ࡶከࡃㄆࡵࡽࢀࡿࡓࡵࠊࠕࠕ㧗㱋⪅࡟౑⏝ࡉࢀࡿ་⸆
ရࡢ⮫ᗋホ౯ἲ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࠖ࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 5 ᖺ 12 ᭶ 2 ᪥௜ࡅ⸆᪂⸆➨ 104
ྕཌ⏕┬⸆ົᒁ᪂་⸆ရㄢ㛗㏻▱㸧ཬࡧࠕࠕ㧗㱋⪅࡟౑⏝ࡉࢀࡿ་⸆ရࡢ⮫ᗋホ౯ἲ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࠖ࡟㛵ࡍࡿ㉁␲ᛂ⟅㞟㸦Q&A㸧࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 22 ᖺ 9 ᭶ 17 ᪥௜ࡅཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ஦ົ㐃⤡㸧ࢆ㋃ࡲ࠼ࡓ᭷ຠᛶཬࡧᏳ඲ᛶࡢ᳨ウࡀᚲせ࡜࡞ࡿࠋ㧗㱋⪅ཬࡧ㠀㧗㱋⪅ࡢ⸆≀ືែࣉࣟࣇ࢓࢖ࣝ➼࡟᫂ࡽ࠿࡞ᕪ␗ࡀ࠶ࡿ࡜⪃࠼ࡽࢀࡿሙྜ࡟
ࡣࠊ㠀㧗㱋⪅㸦65 ṓᮍ‶㸧࡜ࡣู࡟㧗㱋⪅ࢆᑐ㇟࡜ࡋࡓ⮫ᗋヨ㦂ࡀᚲせ࡜࡞ࡿྍ⬟ᛶࡀ࠶ࡿࠋ ⑕౛ᩘࡢタᐃ⿕㦂⪅ᩘࡣࠊ⤫ィᏛⓗ࡞⪃ᐹ࡟ᇶ࡙ࡁࠊヨ㦂┠ⓗࠊ᳨ドࡍ࡭ࡁ௬ㄝཬࡧヨ㦂ࢹࢨ࢖ࣥ࡟ᛂࡌ࡚タᐃࡍࡿࠋ

 ᭷ຠᛶホ౯୍⯡ⓗ࡟୺せ࡞᭷ຠᛶホ౯ࡣࠊಙ㢗ᛶཬࡧጇᙜᛶࡀ᳨ウࡉࢀࠊᅜ㝿ⓗ࡟ᬑཬࡋࡓホ౯ᑻᗘࢆ⏝࠸ࡿࡇ࡜ࡀᚲせ࡛࠶ࡾࠊホ౯᫬࡟࠾ࡅࡿホ౯ᑻᗘࡢ࣮࣋ࢫࣛ࢖ࣥ࠿ࡽࡢኚ໬ࡸᨵၿ⑕
౛ࡢ๭ྜ➼ࢆホ౯࡟⏝࠸ࡿࠋ๪ḟⓗ࡞᭷ຠᛶホ౯ࡣࠊ୺せホ౯㡯┠࡛ᚓࡽࢀࡓ⤖ᯝࡢጇᙜᛶࢆ᳨ウࡍࡿࡔࡅ࡛࡞ࡃࠊᚓࡽࢀࡓ⤖ᯝࡢ⮫ᗋⓗព⩏ࢆ᳨ウࡍࡿࡓࡵ࡟᭷⏝࡛࠶ࡿ 17)ࠋ
ホ౯⪅㛫࡛⤫୍ࡋࡓホ౯ࢆ⾜࠸ࠊホ౯⪅㛫ࡢࡤࡽࡘࡁࢆ᭱ᑠ㝈࡜ࡍࡿࡇ࡜ࡀ࡛ࡁࡿࡼ࠺ࠊ
6㸫㸫ホ౯⪅࡟ᑐࡍࡿᩍ⫱カ⦎➼ࡢ᪉⟇ࢆ᳨ウࡍࡿᚲせࡀ࠶ࡿࠋ≉࡟ࠊᅜ㝿ඹྠヨ㦂࡟࠾࠸࡚ࡣᐇ
᪋ᆅᇦ࡟ࡼࡾホ౯᪉ἲࡀ␗࡞ࡿࡇ࡜ࡀ࡞࠸ࡼ࠺㓄៖ࡍࡿᚲせࡀ࠶ࡿࠋࡲࡓ⮫ᗋヨ㦂㛤ጞ๓࡟ࡣホ౯⪅ࡢ㐺᱁ᛶ࡟ࡘ࠸࡚ࡶホ౯ࡍࡿࡇ࡜ࡀᚲせ࡛࠶ࡿࠋ
 ୺せホ౯㡯┠ ⬨㧊ᦆയ἞⒪࡟࠾ࡅࡿ┿ࡢ┠ᶆࡣࠊ⚄⤒Ꮫⓗᨵၿ࡟࡜࡝ࡲࡽࡎࠊᶵ⬟ணᚋཬࡧ ADL ࢆྵࡴ QOL ࡢᨵၿ࡟࠶ࡿ 18)ࠋ୍᪉ࠊ⌧᫬Ⅼ࡛ࡣ QOL ࡢᨵၿࢆᐈほⓗ࡟ホ౯ࡍࡿࡇ࡜ࡣᅔ㞴࡜⪃࠼ࡽࢀࠊࡲࡓᛴᛶᮇ⬨㧊ᦆയ࡟࠾࠸࡚ࠊ⌧᫬Ⅼ࡛ࡣ QOL ࡜ࡢ㛵㐃ᛶࡀ☜ᐇ࡟❧ドࡉࢀ࡚࠸ࡿ⚄⤒Ꮫⓗ࡞ホ౯ἲࡣᏑᅾࡋ࡞࠸ࡇ࡜࠿ࡽࠊ୺せホ౯㡯┠࡜ࡋ࡚⏝࠸ࡿホ౯ᑻᗘࡣࠊ㐺ษ࡞⚄⤒Ꮫⓗホ౯ࢆタᐃࡍࡿᚲせࡀ࠶ࡿࡀࠊྍ⬟࡛࠶ࢀࡤᶵ⬟ணᚋ࡟㛵ࡍࡿホ౯ࢆタᐃࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ ࡇࢀࡲ࡛࡟ᐇ᪋ࡉࢀࡓ⮫ᗋヨ㦂࡛ࡣࠊASIA scoreࠊAIS ཪࡣ Frankel ศ㢮➼ࢆ᭷ຠᛶࡢホ౯㡯┠࡜ࡋ࡚タᐃࡉࢀࡿࡇ࡜ࡀ୍⯡ⓗ࡛࠶ࡗࡓ 19, 20)ࠋASIA score ࡣ⚄⤒⑕≧ࡢヲ⣽ࢆẚ㍑ⓗ෌⌧ᛶⰋࡃホ౯࡛ࡁࡿࡶࡢࡢ 20)ࠊ᪥ᖖືస࡟࠾ࡅࡿᶵ⬟ࢆ┤᥋♧ࡋ࡚࠸࡞࠸ࠋ୍᪉ࠊAIS
ཬࡧ Frankel ศ㢮ࡣ㯞⑷ࡢᴫ␎ࢆ⡆౽࡟ᢕᥱࡋ࠺ࡿࡓࡵࠊ⮫ᗋୖࡣ᭷⏝࡛࠶ࡾ㢖⏝ࡉࢀࡿࡶࡢࡢࠊᐇ㝿ࡢ ADL ࢆᚲࡎࡋࡶ཯ᫎࡋ࡞࠸࡜ࡢሗ࿌ࡀ࠶ࡾ 21)ࠊAIS ࡀᝏ໬ࡋ࡚࠸ࡿ࡟ࡶ࠿࠿
ࢃࡽࡎ ASIA score ࡀᨵၿࡍࡿ➼ࠊAIS ࡜ ASIA score ࡣ㏫㌿ࡍࡿྍ⬟ᛶࡍࡽ࠶ࡾ࠺ࡿ 22)ࠋ
ホ౯᫬ᮇࡢタᐃ࡟ࡘ࠸࡚ࡣࠊ๓┦ヨ㦂ࡢ⤖ᯝ➼ࢆཧ⪃࡟ࡋࠊ⿕㦂⸆ࡢస⏝ᶵᗎࡸヨ㦂ᐇ᪋ྍ⬟ᛶ➼ࢆ຺᱌ࡋ᳨࡚ウࡍࡿᚲせࡀ࠶ࡿࠋホ౯ࡣ᭱⤊ホ౯᫬Ⅼࡔࡅ࡛ࡣ࡞ࡃࠊ⤒᫬ⓗ᥎⛣ࢆ☜ㄆ࡛ࡁࡿࡼ࠺࡟ࠊ㐺ษ࡞㢖ᗘ࡛ᐇ᪋ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ
 ๪ḟホ౯㡯┠ ๪ḟホ౯㡯┠ࡣࠊ୺せホ౯㡯┠ࢆ⿵㊊ࡍࡿࡓࡵࡢ᭷ຠᛶ࡟㛵ࡍࡿホ౯㡯┠ࢆタᐃࡍࡿࠋࡲࡓࠊ୺せホ౯㡯┠࡜ࡋ࡚ ASIA score ➼ࡢ⚄⤒Ꮫⓗホ౯ࢆタᐃࡋࡓヨ㦂࡟࠾࠸࡚ࡣࠊᶵ⬟ணᚋ࡟㛵ࡍࡿホ౯ࢆタᐃࡍࡿᚲせࡀ࠶ࡿࠋ ๪ḟホ౯㡯┠࡜ࡋ࡚ࡣࠊAIS ࡀ 1 ẁ㝵௨ୖᨵၿࡋࡓ⿕㦂⪅ࡢ๭ྜ➼ࡢ཯ᛂ౛ࡢ๭ྜࡸ NLI
࡞࡝ࡢ⚄⤒Ꮫⓗホ౯ἲཬࡧ EQ5DࠊSF36ࠊSCIM ➼ࡢ ADL/QOL ホ౯ࡢタᐃࢆ᳨ウࡍ࡭ࡁ࡛࠶ࡿࠋ᳨ドⓗヨ㦂࡟࠾࠸࡚ࠊ୺せホ౯㡯┠࡜ࡋ࡚ ASIA score ➼ࡢ⚄⤒Ꮫⓗホ౯ἲࢆタᐃࡋࡓሙྜࠊᶵ⬟ணᚋ࡟㛵ࡍࡿホ౯ࠊADL/QOL ホ౯➼ࡶ๪ḟホ౯㡯┠࡜ࡋ࡚タᐃࡍࡿᚲせࡀ࠶ࡿ 18)ࠋ㏆ᖺ࡛ࡣࠊ⬨㧊ᦆയᝈ⪅࡟࠾ࡅࡿ ADL ホ౯࡜ࡋ࡚ࠊSCIM ࡀ᥎ዡࡉࢀ࡚࠸ࡿ 20)ࠋࡲࡓࠊ㢁㧊ᦆയ࡟࠾࠸࡚ࡣ NLI ࡢୗ㝆ࡣ SCIM ࢭࣝࣇࢣ࢔㡯┠࡜ࡢ┦㛵ࡀ࠶ࡿ࡜ሗ࿌ࡉࢀ࡚࠸ࡿ 23)ࠋ⬨㧊ᦆയ࡛ࡣ⭤⬔┤⭠㞀ᐖࢆࡁࡓࡋࠊࡇࢀࡽࡢ⑕≧ࡶ⿕㦂⪅ࡢ ADL/QOL ࢆⴭࡋࡃᦆ࡞࠺
ሙྜࡀ࠶ࡿࡢ࡛ࠊ⭤⬔┤⭠㞀ᐖ࡟ࡘ࠸࡚ࡶࠊSCIM ࡢୗ఩㡯┠➼ࠊ㐺ษ࡞ホ౯ᣦᶆࢆ⏝࠸࡚ホ౯ࡍࡿࡇ࡜ࢆ᳨ウࡍ࡭ࡁ࡛࠶ࡿࠋࡲࡓࠊ⬨㧊㞀ᐖᛶ⑊③ࢆྵࡴ⑊③ࡢホ౯ࡶ㔜せ࡛࠶ࡿࡓࡵࠊ㐺ษ࡞ホ౯ᣦᶆࢆ⏝࠸࡚ホ౯ࡍࡿࡇ࡜ࢆ᳨ウࡍ࡭ࡁ࡛࠶ࡿࠋ
7㸫㸫

 Ᏻ඲ᛶホ౯᭷ᐖ஦㇟࡜ࡣࠊ་⸆ရ㸦⿕㦂⸆ࢆྵࡴࠋ௨ୗࡇࡢ㡯࡟࠾࠸࡚ྠࡌࠋ
㸧ࢆᢞ୚ࡉࢀࡓᝈ⪅ཪࡣ⿕㦂⪅࡟⏕ࡌࡓ࠶ࡽࡺࡿዲࡲࡋࡃ࡞࠸་⒪ୖࡢ࡛ࡁࡈ࡜࡛࠶ࡾࠊᙜヱ་⸆ရࡢᢞ୚࡜ࡢ
ᅉᯝ㛵ಀࡢ᭷↓ࡣၥࢃ࡞࠸ࠋࡘࡲࡾࠊ་⸆ရࡀᢞ୚ࡉࢀࡓ㝿࡟㉳ࡇࡿࠊ࠶ࡽࡺࡿዲࡲࡋࡃ࡞
࠸ࠊཪࡣពᅗࡋ࡞࠸ᚩೃ㸦⮫ᗋ᳨ᰝ್ࡢ␗ᖖࢆྵࡴ㸧ࠊ⑕≧ཪࡣ⑓Ẽࡢࡇ࡜࡛࠶ࡿࠋ᭷ᐖ஦
㇟ࡀㄆࡵࡽࢀࡓሙྜࡣࠊ⑕౛ሗ࿌᭩࡟஦㇟ྡࠊ㔜⑕ᗘࠊ㌿ᖐࠊⓎ⌧ཬࡧ㌿ᖐࡀ☜ㄆࡉࢀࡓ᫬
ᮇࠊ⿕㦂⸆࣭ᑐ↷⸆ࡢ᭹⸆≧ἣ୪ࡧ࡟ฎ⨨ࡢ᭷↓ཬࡧࡑࡢෆᐜ➼ࢆグ㘓ࡍࡿ࡜࡜ࡶ࡟ࠊ㔜⠜࡞᭷ᐖ஦㇟࠿ྰ࠿ࠊཬࡧ⿕㦂⸆࣭ᑐ↷⸆࡜ࡢᅉᯝ㛵ಀࢆุᐃࡍࡿࠋࡑࢀࡒࢀࡢ஦㇟࡟࠾ࡅࡿ
㔜⑕ᗘศ㢮࡜ࡋ࡚ࡣࠊ㍍ᗘࠊ୰➼ᗘࠊ㧗ᗘࢆ⏝࠸ࡿࠋ
ࡲࡓࠊCIOMS VI Working Group ࡛ࡣࠊ⑕౛ሗ࿌᭩࡬ࡢ᭷ᐖ஦㇟ྡࡢグ㍕ࢆಶࠎࡢ⑕≧࣭ᚩೃ࡛ࡣ࡞ࡃࠊྍ⬟࡞㝈ࡾデ᩿ྡ࡜ࡍࡿࡇ࡜ࡀᥦゝࡉࢀ࡚࠸ࡿ 24)ࠋࡲࡓࠊMedDRA ࡢ Point
to Consider ࡟࠾࠸࡚ࡶࠊ᭷ᐖ஦㇟ࡢሗ࿌᪉ἲ࡟ࡘ࠸࡚ࠊデ᩿ྡࡀ⑕≧࣭ᚩೃࢆໟྵࡋ࡚࠸ࡿ
ࡢ࡛࠶ࢀࡤࠊ᝟ሗࡢ႙ኻ࡟ࡣᙜࡓࡽ࡞࠸࡜᭩࠿ࢀ࡚࠸ࡿ 25)ࠋࡓࡔࡋࠊὀ┠ࡍ࡭ࡁ≉ᐃࡢ⑕≧࣭ᚩೃࡀᏑᅾࡍࡿ➼ࠊ᭷ᐖ஦㇟ྡ࡜ࡋ࡚ࡢデ᩿ྡ࡜ࡣู࡟ࠊಶࠎࡢ⑕≧ྡ࣭ᚩೃྡࢆ཰㞟ࡋホ౯ࡍࡿࡇ࡜ࡀ㔜せ࡞ሙྜࡀ࠶ࡿࡇ࡜࡟␃ពࡍ࡭ࡁ࡛࠶ࡿࠋヲ⣽ࡣࠊࠕ἞㦂ࡢ⥲ᣓሗ࿌᭩ࡢᵓᡂ࡜ෆᐜ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࠖ㸦ᖹᡂ 8 ᖺ 5 ᭶ 1 ᪥௜ࡅ⸆ᑂ➨ 335 ྕཌ⏕┬⸆ົᒁᑂᰝㄢ㛗㏻▱㸧ཬࡧࠕࠕ἞㦂ࡢ⥲ᣓሗ࿌᭩ࡢᵓᡂ࡜ෆᐜ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࠖ࡟㛵ࡍࡿ㉁␲ᛂ⟅㞟㸦Q&A㸧ࠖ㸦ᖹᡂ 24 ᖺ 10 ᭶ 18 ᪥௜ࡅཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ஦ົ㐃⤡㸧ࢆཧ↷ࡉࢀࡓ࠸ࠋ
⮫ᗋヨ㦂࡛ࡣࠊ⿕㦂⸆࡟≉ᚩⓗ࡞᭷ᐖ஦㇟࡟ຍ࠼࡚ࠊᛴᛶᮇ⬨㧊ᦆയࡢ⑓ែ࡟㛵㐃ࡍࡿ௨ୗࡢࡼ࠺࡞᭷ᐖ஦㇟࡟ࡘ࠸࡚ࡶὀ┠ࡋ࡚཰㞟ࡍ࡭ࡁ࡛࠶ࡿࠋ
㔜せ࡞᭷ᐖ஦㇟
ձ 㯞⑷ࡢᝏ໬
ղ ⫵⅖
ճ ࿧྾୙඲մ ῝㒊㟼⬦⾑ᰦ⑕㸭⫵᱾ሰյ ⸆๣ᛶ㐣ᩄ⑕⑕ೃ⩌ն ᒀ㊰ឤᰁ⑕
շ 〟⒔
ո 㛵⠇ᣊ⦰չ ⬨㧊㞀ᐖᛶ⑊③պ ᾘ໬⟶₽⒆
ջ ⬻᱾ሰռ ㉳❧ᛶప⾑ᅽ8㸫㸫

 ే⏝⚗Ṇ⸆ཬࡧే⏝⚗Ṇ⒪ἲࡢタᐃ ే⏝⚗Ṇ⸆᭷ຠᛶホ౯࡟ᙳ㡪ࢆ୚࠼ࡿྍ⬟ᛶࡢ࠶ࡿ⸆๣࡟ࡘ࠸࡚ࡣࠊ஦๓࡟೔⌮ⓗ࣭⮫ᗋⓗ࡟ၥ㢟ࡀ࡞࠸࠿ࢆ᳨ウࡋࡓୖ࡛ࠊྍ⬟࡞㝈ࡾే⏝⚗Ṇ࡜ࡍ࡭ࡁ࡛࠶ࡿࠋ೔⌮ⓗ࣭⮫ᗋⓗ࡟ၥ㢟ࡀ࠶ࡾే⏝⚗Ṇ⸆࡟タᐃ࡛ࡁ࡞࠸⸆๣࡟ࡘ࠸࡚ࡶࠊ⿕㦂⸆ࡢホ౯࡟ᙳ㡪ࢆཬࡰࡉ࡞࠸ࡼ࠺ࠊヨ㦂ᮇ㛫୰ࡣ⏝ἲ࣭⏝㔞㸦㡻⏝ࡢሙྜࡣ౑⏝㢖ᗘ㸧ࢆኚ᭦ࡋ࡞࠸ࡼ࠺つᐃࡍࡿ➼ࡢᑐᛂࡀᚲせ࡛࠶ࡿࠋ ే⏝⚗Ṇ⒪ἲ
ࣜࣁࣅࣜࢸ࣮ࢩࣙࣥࡀ┤᥋ཷയࡋࡓ⬨㧊ࢆಟ᚟ࡉࡏࡿࠊཪࡣ෌⏕ࡉࡏࡿ࡜࠸ࡗࡓ࢚ࣅࢹ
ࣥࢫࡣ࡞࠸ࡀࠊࣜࣁࣅࣜࢸ࣮ࢩࣙࣥᐇ᪋ࡢ᭷↓ࡸෆᐜࡣᶵ⬟ணᚋ࡟ᙳ㡪ࢆ୚࠼ࡿྍ⬟ᛶࡀ࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊ᪋タ㛫࣭⿕㦂⪅㛫ࡢࣜࣁࣅࣜࢸ࣮ࢩࣙࣥࡢᕪ␗ࡀ᭷ຠᛶホ౯࡟୚࠼ࡿᙳ
㡪ࢆྍ⬟࡞㝈ࡾపῶ࡛ࡁࡿࡼ࠺ࠊࣜࣁࣅࣜࢸ࣮ࢩࣙࣥࡢᐇ᪋ෆᐜ࡟㛵ࡋ࡚ࡣ୍ᐃࡢᇶ‽ࢆタࡅࡿᚲせࡀ࠶ࡿࠋ
ࡲࡓࠊᡭ⾡᪋⾜ࡀ᭷ຠᛶཬࡧᏳ඲ᛶࡢホ౯࡟୚࠼ࡿᙳ㡪࡟ࡘ࠸࡚ࡣࠊ⌧᫬Ⅼ࡛ࡣ୙࡛᫂࠶
ࡿࡇ࡜ࢆ㋃ࡲ࠼ࠊ⮫ᗋヨ㦂ᮇ㛫୰ࡢᡭ⾡ࡢྍྰ࡟ࡘ࠸࡚ࡣࠊணࡵ᳨ウࢆ⾜࠸ࠊᡭ⾡ᐇ᪋ࡢᇶ‽➼ࢆྵࡵ࡚㐺ษ࡟つᐃࡍࡿᚲせࡀ࠶ࡿࠋ
 ࡑࡢ௚ࡢ␃ព஦㡯 ヨ㦂ᐇ᪋యไ
ᛴᛶᮇ⬨㧊ᦆയ࡟࠾ࡅࡿ⮫ᗋヨ㦂࡛ࡣࠊ⿕㦂⪅ࡣᩆᛴᝈ⪅࡛࠶ࡾࠊ⮫ᗋヨ㦂࡟࠾ࡅࡿ⑕౛
Ⓩ㘓ࡣィ⏬ⓗ࡟⾜࠼࡞࠸ࡓࡵࠊᅵ᪥⚃⚍᪥ࡸኪ㛫ࢆྵࡵ࡚᪩ᛴ࠿ࡘ㐺ษ࡟ᑐᛂྍ⬟࡞యไ
ཬࡧᝈ⪅Ⓩ㘓ᡭ㡰ࢆᩚഛࡍࡿࡇ࡜ࡀ᥎ዡࡉࢀࡿࠋ⮫ᗋヨ㦂ཧຍࡢྠពྲྀᚓ࡟࠾࠸࡚ࡣࠊཷയ
ᚋࡢ⢭⚄ⓗ࡟ࡶ୙Ᏻᐃ࡞ᝈ⪅ཬࡧᐙ᪘࡟ៅ㔜࡞㓄៖ࡀᚲせ࡛࠶ࡿࠋ ⮫ᗋヨ㦂ᮇ㛫ࡀᩘࣨ᭶௨ୖ࡟࠾ࡼࡪሙྜࠊᛴᛶᮇ⑓㝔࠿ࡽᅇ᚟ᮇࣜࣁࣅࣜࢸ࣮ࢩࣙࣥ⑓㝔࡬ࡢ㌿㝔ࠊࡲࡓࡉࡽ࡞ࡿ㌿㝔➼࡟ࡼࡾ⿕㦂⪅ࡢ㏣㊧ࡀᅔ㞴࡜࡞ࡿࡇ࡜ࡀ⪃࠼ࡽࢀࡿࠋࡋࡓ
ࡀࡗ࡚ࠊ୺せ࡞ホ౯ࡢ᫬Ⅼ࡟࠾ࡅࡿࢹ࣮ࢱࡢḞ ࡀྍ⬟࡞㝈ࡾⓎ⏕ࡋ࡞࠸ࡼ࠺ࠊணࡵ᳨ウࡍ
ࡿᚲせࡀ࠶ࡿࠋ࡞࠾ࠊ㌿㝔ඛࡢ་⒪ᶵ㛵࡛⮫ᗋヨ㦂࡟㛵ࡍࡿࢹ࣮ࢱࢆ཰㞟ࡍࡿሙྜ࡟ࡣࠊᙜ
ヱᶵ㛵ࡶ⮫ᗋヨ㦂ᐇ᪋᪋タ࡜ࡋ࡚ྲྀࡾᢅ࠺ᚲせࡀ࠶ࡿྍ⬟ᛶࡀ࠶ࡿࡓࡵࠊ␃ពࡍࡿࡇ࡜ࠋ
 ⿕㦂⪅⫼ᬒࡢグ㘓⬨㧊ᦆയࡣᦆയ㧗఩࣭㔜⑕ᗘ࡟ࡼࡾ㠀ᖖ࡟ከᙬ࡞⑕≧⤒㐣ࢆ♧ࡍࠋ⿕㦂⸆ࡢ≉ᛶࡸヨ㦂ࡢ┠ⓗ࡟ᛂࡌ࡚ࠊ᭱᪂ࡢ⛉Ꮫⓗ▱ぢࡶ㋃ࡲ࠼ࠊ㐺ษ࡟⿕㦂⪅⫼ᬒ࡟㛵ࡍࡿ᝟ሗ཰㞟ࢆ⾜࠸ࠊグ㘓ࡍࡿᚲせࡀ࠶ࡿࠋ⫼ᬒᅉᏊࡢ౛࡜ࡋ࡚ࠊᦆയ࠿ࡽࡢ⤒㐣ᮇ㛫ࠊᦆയ㧗఩ࠊ㔜⑕ᗘࠊᡭ⾡᪋⾜ࡢ᭷↓ࠊᖺ㱋ࠊᦆയࡢཎᅉ➼ࡀᣲࡆࡽࢀࡿࠋࡇࢀࡽྛ⿕㦂⪅⫼ᬒࢆ⤌ධࢀ᫬࡟࡝ࡢ⛬ᗘ⪃9㸫㸫

៖ࡍࡿ࠿ࡣࠕ2.1. ᑐ㇟㞟ᅋࠖࡢ㡯ࢆཧ↷ࡉࢀࡓ࠸ࠋ
 ⮫ᗋヨ㦂ᮏ㡯࡛ࡣ㛤Ⓨࡢྛẁ㝵࡟࠾࠸࡚ᐇ᪋ࡉࢀࡿ⮫ᗋヨ㦂ィ⏬ࡢ␃ពⅬࢆㄝ᫂ࡍࡿࠋ୍⯡࡟ࡣࠊ⮫ᗋ⸆⌮ヨ㦂ࠊ᥈⣴ⓗヨ㦂ࠊ᳨ドⓗヨ㦂ࡢ㡰࡟㐍ࡳࠊ⮫ᗋ⸆⌮ヨ㦂࡛ࡣ⸆≀ືែࠊᏳ඲ᛶཬ
ࡧ⏝ἲ࣭⏝㔞ࡢ᳨ウࠊ᥈⣴ⓗヨ㦂࡛ࡣ POC ࡢ☜❧ࠊ⏝ἲ࣭⏝㔞ཬࡧ」ᩘࡢ᭷ຠᛶᣦᶆࡢ᳨
ウࠊ᳨ドⓗヨ㦂࡛ࡣ᭱ࡶ௦⾲ⓗ࡞ᣦᶆ࡟࡚᭷ຠᛶࡢ᳨ドཬࡧᏳ඲ᛶࡢ᳨ウࢆ⾜࠺ࠋ๓㏙ࡋࡓෆᐜࡣࠊ඲⑌ᝈ㡿ᇦ࡟㛵ࡍࡿ⥲ㄽ࡛࠶ࡿࡓࡵࠊヲࡋࡃࡣࠊICH ࢞࢖ࢻࣛ࢖ࣥࢆཧ↷ࡉࢀࡓ࠸ࠋ
 ⮫ᗋ⸆⌮ヨ㦂  ┠ⓗ ୍⯡࡟ࡣࠊୡ⏺࡛ึࡵ࡚⿕㦂⸆ࢆࣄࢺ࡟ᢞ୚ࡍࡿሙྜࡣࠊᏳ඲ᛶホ౯ࢆ୺ࡓࡿ┠ⓗ࡟ࡍࡿࡓࡵࠊ㠀⮫ᗋヨ㦂࡛ᚓࡽࢀࡓ᝟ሗࢆඖ࡟ࠊ೺ᗣᡂே⏨ᛶࢆ⿕㦂⪅࡜ࡋࡓ⮫ᗋ⸆⌮ヨ㦂ࢆ⾜࠺ࠋ᪤ᢎㄆ་⸆ရࡢ㐺ᛂᣑ኱ࡢ㛤Ⓨ࡛ࡣ┬␎࡛ࡁࡿሙྜࡀ࠶ࡿࡀࠊ⏝㔞࣭ᢞ୚⤒㊰ࡀ᪤ᢎㄆရ࡜
኱ࡁࡃ␗࡞ࡿሙྜࡣ⮫ᗋ⸆⌮ヨ㦂ࡢᐇ᪋ࡀᚲせ࡜࡞ࡿࠋ⮫ᗋ⸆⌮ヨ㦂ࡣࠊ⿕㦂⸆ࢆࣄࢺ࡟ᢞ
୚ࡍࡿ㝿ࡢᏳ඲࡞⏝㔞ࠊᢞ୚᪉ἲࡢ᳨ウࢆ୺࡞┠ⓗ࡜ࡍࡿࠋࡲࡓࠊ⿕㦂⸆ࡢ⸆≀ືែᏛⓗࣉࣟࣇ࢓࢖ࣝࡢ᳨ウࡶ⾜࠺ࠋ ヨ㦂ィ⏬࡟㛵ࡍࡿ␃ពⅬ 
ẚ㍑ⓗᑡேᩘࢆᑐ㇟࡜ࡋࠊ▷ᮇ㸦ཎ๎࡜ࡋ࡚ࠊ༢ᅇཪࡣ཯᚟ᢞ୚㸧ࡢ⿕㦂⸆ࡢᢞ୚ࢆ⾜࠺ࠋ
㏻ᖖࡣࠊヨ㦂ᮇ㛫୰ࠊ⿕㦂⪅ࡣධ㝔ཪࡣࡑࢀ࡟‽ࡌࡓ≧ែ࡛ᐇ᪋ࡍࡿࠋ⏝ἲ࡟ࡘ࠸࡚ࡣࠊ⮫ᗋ⌧ሙ࡛ࡢ౑⏝᪉ἲࢆ⪃៖ࡋタᐃࡍࡿࠋ࡞࠾ࠊ⿕㦂⸆ࡢ⸆⌮స⏝ࡢୖ࡛ࠊ೺ᗣᡂே࡬ࡢᢞ୚
ࡀᏳ඲ᛶୖ኱ࡁ࡞ၥ㢟࡜࡞ࡿሙྜࠊ౵くᛶࡢ㧗࠸ᡭᢏࢆ⏝࠸⿕㦂⸆ࢆᢞ୚ࡍࡿሙྜ➼࡟ࡣࠊᝈ⪅ࢆᑐ㇟࡜ࡍࡿࡇ࡜ࡀ㐺ษ࡛࠶ࡿሙྜࡶ࠶ࡿࠋࡑࡢ㝿ࠊ᭷ຠᛶཬࡧᏳ඲ᛶࢆணഛⓗ࡟᳨ウࡍࡿ➨ I/II ┦ヨ㦂࡜ࡋ࡚ᐇ᪋ࡍࡿࡇ࡜ࡶ⪃࠼ࡽࢀࡿࡀࠊᏳ඲ᛶࡢ☜ㄆ࡟᭱ࡶ㔜Ⅼࢆ࠾ࡃࠋ⏝ἲ࣭⏝㔞࡜ࡋ࡚㠀⮫ᗋヨ㦂ᡂ⦼࠿ࡽ᥎ᐃࡉࢀࡿᏳ඲࡞᭱ప⏝㔞ࡢ༢ᅇᢞ୚࠿ࡽ㛤ጞࡋࠊᏳ඲
ᛶࢆ☜ㄆࡋ࡞ࡀࡽࠊᑗ᮶ண

ࡉࢀࡿ⏝㔞௨ୖࡲ࡛₞ḟቑ㔞ࡉࡏࡿࠋ࡞࠾ࠊࣄࢺ࡟ึࡵ࡚ᢞ୚

ࡍࡿሙྜ➼࡛ࡣࠊᚲせ࡟ᛂࡌ࡚ࠕࠕ་⸆ရ㛤Ⓨ࡟࠾ࡅࡿࣄࢺึᅇᢞ୚ヨ㦂ࡢᏳ඲ᛶࢆ☜ಖࡍࡿࡓࡵࡢ࢞࢖ࢲࣥࢫࠖ࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 24 ᖺ 4 ᭶ 2 ᪥௜ࡅ⸆㣗ᑂᰝⓎ 0402 ➨ 1 ྕཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧ཬࡧࠕࠕ་⸆ရ㛤Ⓨ࡟࠾ࡅࡿࣄࢺึᅇᢞ୚ヨ㦂ࡢᏳ඲ᛶࢆ☜ಖࡍࡿࡓࡵࡢ࢞࢖ࢲࣥࢫ࡟㛵ࡍࡿ㉁␲ᛂ⟅㞟㸦Q&A㸧ࠖ࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 24 ᖺ 4 ᭶ 2᪥௜ࡅཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ஦ົ㐃⤡㸧ࢆཧ↷ࡉࢀࡓ࠸ࠋ
Ᏻ඲ᛶホ౯࡜ࡋ࡚ࡣࠊ⿕㦂⸆࡟ᛂࡌ࡚ᚲせ࡞㡯┠ࢆタᐃࡍࡿࠋ⮫ᗋヨ㦂ᮇ㛫୰࡟Ⓨ⏕ࡋࡓ⮫ᗋ᳨ᰝ್␗ᖖࢆⓎぢࡍࡿࡓࡵ࡟ࡣࠊ㐺ษ࡞᳨ᰝࢆ⿕㦂⸆ᢞ୚㛤ጞ๓ᚋ࡟⾜࠺ᚲせࡀ࠶ࡿࠋ

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10
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㸫㸫

 ࡑࡢ௚ࡢ␃ព஦㡯㧗㱋⪅㸦65 ṓ௨ୖ㸧ࠊࡲࡓ⿕㦂⸆ࡢ⸆≀ືែୖࡢ≉ᚩ࡟ࡼࡾ⫢ᶵ⬟㞀ᐖᝈ⪅ࠊ⭈ᶵ⬟㞀ᐖᝈ⪅➼ࢆᑐ㇟࡜ࡋࡓ᳨ウࡀᚲせ࡞ሙྜࡀ࠶ࡿࠋ
⸆≀┦஫స⏝ࡀண ࡉࢀࡿሙྜࡣࠊ≉ᐃࡢ⸆≀࡜ࡢే⏝࡟ࡼࡿ᳨ウࡶᚲせ࡞ሙྜࡀ࠶ࡿࠋヲ⣽ࡣࠊࠕ་⸆ရࡢ⮫ᗋ⸆≀ືែヨ㦂࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 13 ᖺ 6 ᭶ 1 ᪥௜ࡅ་⸆ᑂⓎ➨ 796
ྕཌ⏕ປാ┬་⸆ᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧ཬࡧࠕࠕ་⸆ရ㛤Ⓨ࡜㐺ṇ࡞᝟ሗᥦ౪ࡢࡓࡵࡢ⸆≀┦஫స⏝࢞࢖ࢻࣛ࢖ࣥࠖ࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 30 ᖺ 7 ᭶ 23 ᪥௜ࡅ⸆⏕⸆ᑂⓎ 0723 ➨ 4 ྕཌ⏕ປാ┬་⸆࣭⏕ά⾨⏕ᒁ་⸆ရᑂᰝ⟶⌮ㄢ㛗㏻▱㸧ࢆཧ↷ࡉࢀࡓ࠸ࠋ
ࡲࡓࠊࡑࡢ௚ࠊࠕ㠀ᢠ୙ᩚ⬦⸆࡟࠾ࡅࡿQT/QTc㛫㝸ࡢᘏ㛗࡜ദ୙ᩚ⬦స⏝ࡢ₯ᅾⓗྍ⬟ᛶ࡟㛵ࡍࡿ⮫ᗋⓗホ౯࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ21ᖺ10᭶23᪥௜ࡅ⸆㣗ᑂᰝⓎ1023➨㸯ྕཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧࡟࠾࠸࡚つᐃࡉࢀࡿQT/QTcホ౯ヨ㦂➼ࡢᚲせ࡞⮫ᗋ⸆⌮
ヨ㦂ࢆࠊ㛵㐃࢞࢖ࢻࣛ࢖ࣥࢆ㋃ࡲ࠼࡚㐺ษ࡟ᐇ᪋ࡍࡿᚲせࡀ࠶ࡿࠋ
 ᥈⣴ⓗヨ㦂 ┠ⓗ᥈⣴ⓗヨ㦂ࡢ┠ⓗࡣࠊ⮫ᗋ⸆⌮ヨ㦂࡛Ᏻ඲ᛶࡀ☜ㄆࡉࢀࡓ⸆≀࡟ࡘ࠸࡚ࠊᝈ⪅ࢆᑐ㇟࡜ࡋ
࡚ POC ࢆ☜❧ࡍࡿࡇ࡜ࠊ⏝㔞཯ᛂ㛵ಀࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࠊ᳨ドⓗヨ㦂࡟࠾ࡅࡿ⏝ἲ࣭⏝㔞ࠊホ౯㡯┠ཬࡧホ౯ᮇ㛫ࢆỴᐃࡍࡿࡇ࡜➼࡟࠶ࡿࠋ
 ヨ㦂ィ⏬࡟㛵ࡍࡿ␃ពⅬ᥈⣴ⓗヨ㦂࡛⏝㔞཯ᛂ㛵ಀࢆ᳨ウࡍࡿሙྜࡢヨ㦂ࢹࢨ࢖ࣥࡣࠊ⌧≧࡛ࡣࣉࣛࢭ࣎ࢆᑐ↷࡜ࡋ࡚ࠊ」ᩘࡢ⏝㔞⩌ࢆᅛᐃ⏝㔞࡛タᐃࡋࡓ↓సⅭ໬஧㔜┣᳨୪⾜⩌㛫ẚ㍑ヨ㦂࡜ࡍ࡭ࡁ࡛࠶ࡿࠋ⏝ἲ࡟ࡘ࠸࡚ࡣࠊ⮫ᗋ⌧ሙ࡛ࡢ౑⏝᪉ἲࢆ⪃៖ࡋࠊᢞ୚ᮇ㛫࡟ࡘ࠸࡚ࡶ᳨ドⓗヨ㦂ࡢィ⏬࡟㝿ࡋ࡚ᚲせ࡞᝟ሗࡢ཰㞟ࡀ࡛ࡁࡿࡼ࠺࡟㐺ษ࡟タᐃࡍࡿࠋ
⿕㦂⸆ࡀ௚ࡢຠ⬟࣭ຠᯝ࡛᪤࡟ᢎㄆࡉࢀ࡚࠸ࡿሙྜ࡛࠶ࡗࡓ࡜ࡋ࡚ࡶࠊ⮫ᗋヨ㦂ࡢホ౯ᣦᶆཬࡧ࣋ࢿࣇ࢕ࢵࢺ࣭ࣜࢫࢡࣂࣛࣥࢫホ౯➼ࡣ⑌ᝈẖ࡟␗࡞ࡿࡓࡵࠊ᭱ᑠ᭷ຠ⏝㔞ཬࡧ⮳㐺⏝㔞ࡣ␗࡞ࡿྍ⬟ᛶࡀ࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊࡇࡢࡼ࠺࡞ሙྜ࡛࠶ࡗࡓ࡜ࡋ࡚ࡶ㐺ษ࡟᭱ᑠ᭷ຠ
⏝㔞ཬࡧ⮳㐺⏝㔞ࢆ᳨ウࡍ࡭ࡁ࡛࠶ࡿࠋ
᥈⣴ⓗヨ㦂࡛ࡣࠊ⬨㧊ᦆയࡢணᚋ࡟ᙳ㡪ࢆ୚࠼࠺ࡿ⿕㦂⪅⫼ᬒࢆ㝈ᐃࡍࡿ➼ࡢ᪉⟇࡟ࡼࡾࠊ⩌㛫ᕪࡢ᫂░໬࡟ᕤኵࢆࡋࡓ㞟ᅋ࡟࠾࠸࡚᭷ຠᛶホ౯ࢆ᳨ウࡍࡿࡇ࡜ࡶ୍᱌࡛࠶ࡿࠋ
 ᳨ドⓗヨ㦂 ┠ⓗ
᳨ドⓗヨ㦂ࡢ┠ⓗࡣࠊ᥈⣴ⓗヨ㦂࡟ࡼࡗ࡚ࠊ᭷ຠᛶཬࡧᏳ඲ᛶࡀ᳨ウࡉࢀࠊ⮫ᗋ⏝ἲ࣭⏝㔞ࡀ᥎ᐃࡉࢀࡓ⸆≀࡟ࡘ࠸࡚ࠊ᭷ຠᛶࢆ᳨ドࡋࠊᏳ඲ᛶࢆ☜ㄆࡍࡿࡇ࡜࡟࠶ࡿࠋ 11㸫㸫

 ヨ㦂ィ⏬࡟㛵ࡍࡿ␃ពⅬ 
᳨ドⓗヨ㦂࡛ࡣࣉࣛࢭ࣎࡟ᑐࡍࡿඃ㉺ᛶࢆ᳨ドࡍࡿᚲせࡀ࠶ࡿࠋ࡞࠾ࠊ⌧᫬Ⅼ࡛ࡣᛴᛶᮇ
⬨㧊ᦆയࢆᑐ㇟࡜ࡋࡓᶆ‽἞⒪ࡀ☜❧ࡉࢀ࡚࠸࡞࠸ࡓࡵࠊ⌧≧࡛ࡣࣉࣛࢭ࣎ࡢタᐃ࡟ࡣ೔⌮ୖࡢ኱ࡁ࡞ၥ㢟ࡣ࡞࠸࡜⪃࠼ࡽࢀࡿࠋ
ࣉࣛࢭ࣎ࢆ౑⏝ࡍࡿ㝿ࡣࠊࣉࣛࢭ࣎ࡢࠕእぢࠖࠊࠕ࡟࠾࠸࣭࿡ࠖ➼ࡀ⿕㦂⸆࡜㆑ู୙⬟࡛࠶ࡿ࡭ࡁ࡛࠶ࡿࠋ࡞࠾ࠊὀᑕ๣➼࡛⿕㦂⸆࡜ࡢ㆑ูࡀ୙ྍ⬟࡞㐺ษ࡞ࣉࣛࢭ࣎ࢆ〇㐀࡛ࡁ࡞࠸ሙྜࡸࠊ౵くᛶࡀ㧗࠸ᡭᢏ࡛ࡢᢞ୚ࡀᚲせ࡜࡞ࡿሙྜ࡛ࠊࢩ࣒ࣕࡢ౑⏝ࡀ㐺ᙜ࡜⪃࠼ࡽࢀࡿሙྜ࡟ࡣࠊ⸆๣ᢞ୚ࢆ⾜࠺㠀┣᳨་ᖌࢆタᐃࡋࡓୖ࡛ࠊ⿕㦂⪅ࠊ᭷ຠᛶཬࡧᏳ඲ᛶ
ホ౯ࢆ⾜࠺་ᖌࠊࡑࡢ௚ࡢ⮫ᗋヨ㦂ᢸᙜ⪅ࢆ┣᳨ୗ࡟࠾ࡃ᪉ἲ➼࡟ࡼࡾ┣᳨ᛶࢆᢸಖࡍࡿ
ࡇ࡜ࡀྍ⬟࡞ሙྜࡀ࠶ࡿࠋࡲࡓࠊ౛࠼ࡤࠊ⮫ᗋヨ㦂࡛⏝࠸ࡿ⿕㦂⸆ࡢ≉ᛶ࡟ࡼࡾ⮫ᗋ᳨ᰝ್➼ࡀከࡃࡢ⿕㦂⪅࡛ኚືࡍࡿ࡜⪃࠼ࡽࢀࡿ⸆๣ࡢሙྜࠊᙜヱ⮫ᗋ᳨ᰝ್➼ࢆ▱ࡿࡇ࡜࡟ࡼࡗ࡚┣᳨ᛶࡀ◚⥢ࡍࡿྍ⬟ᛶࡀ࠶ࡿࡇ࡜࠿ࡽࠊ┣᳨ୗࡢ⮫ᗋヨ㦂ᢸᙜ⪅࡟ࡣᙜヱ᳨ᰝ್➼ࢆ▱ࡽࢀ࡞࠸ࡼ࠺࡟ࡍࡿ➼ࡢ㓄៖ࡀᚲせ࡟࡞ࡿࠋ
 〇㐀㈍኎ᚋㄪᰝ➼ ᛴᛶᮇ⬨㧊ᦆയࡢ἞⒪ࢆ┠ⓗ࡜ࡋࡓ་⸆ရ➼ࡢホ౯࡟࠾࠸࡚ࠊ㛗ᮇⓗ࡞ணᚋࢆホ౯ࡍࡿࡇ࡜ࡣ㔜せ࡛࠶ࡾࠊẚ㍑ⓗ▷ᮇ࠿ࡘᑠつᶍࡢ⮫ᗋヨ㦂ࡢࡳ࡛ࡣ㝈⏺ࡀ࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊ〇㐀㈍኎ᚋ࡟ࡣࠊ་⸆ရ➼ࡢ≉ᛶࠊᏳ඲ᛶࣉࣟࣇ࢓࢖ࣝ➼ࢆ㋃ࡲ࠼ࠊ㐺ษ࡞ࣜࢧ࣮ࢳࢡ࢚ࢫࢳࣙࣥࢆタᐃࡋࡓୖ࡛ࠊ〇㐀㈍኎ᚋㄪᰝ➼ࢆᐇ᪋ࡋࠊ⮫ᗋヨ㦂࡟࠾࠸࡚᫂ࡽ࠿࡟࡞ࡽ࡞࠿ࡗࡓ
Ⅼ࡟ࡘ࠸࡚᝟ሗ཰㞟ࡍࡿᚲせࡀ࠶ࡿࠋ࡞࠾ࠊ〇㐀㈍኎ᚋㄪᰝ➼ࡢᐇ᪋ィ⏬࡟ࡘ࠸࡚ࡣࠊࠕ〇㐀㈍኎ᚋㄪᰝ➼ࡢᐇ᪋ィ⏬ࡢ⟇ᐃ࡟㛵ࡍࡿ᳨ウࡢ㐍ࡵ᪉࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 30 ᖺ 1 ᭶ 31 ᪥௜ࡅබ⾲ ་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ㸧ࡶཧ↷ࡉࢀࡓ࠸ࠋ
 ⏝ㄒ࣭␎ㄒ
␎ྕ࣭␎グ

ⱥㄒ⾲グ

ADL

Activity of Daily Living

AIS

ASIA Impairment Scale

ASIA

American Spinal Injury Association

CIOMSFAS
ICH

᪥ᮏㄒ⾲グ
᪥ᖖ⏕άືస
⡿ᅜ⬨㧊ᦆയᏛ఍ᶵ⬟㞀ᐖศ㢮

Council for International Organizations of Medical
Science
Full Analysis Set⡿ᅜ⬨㧊ᦆയᏛ఍
ᅜ㝿་Ꮫᅋయ༠㆟఍᭱኱ࡢゎᯒᑐ㇟㞟ᅋ

International Council for Harmonization of TechnicalRequirements for Pharmaceuticals for human use ་⸆ရつไㄪ࿴ᅜ㝿఍㆟

ITT

Intention-To-Treat-

MedDRA

Medical Dictionary for Regulatory Activities ICH ᅜ㝿་⸆⏝ㄒ㞟12㸫㸫



Terminology
NLI

Neurological Level of Injury⚄⤒Ꮫⓗᦆയ㧗఩

PMDA

Pharmaceuticals and Medical Devices Agency:

་⸆ရ་⒪ᶵჾ⥲ྜᶵᵓ

POC

Proof Of Concept◊✲௬ㄝࡀᐇドࡉࢀࡿࡇ࡜ࠋPPSPer Protocol Set

QOLQuality Of Lifeே⏕࣭⏕άࡢ㉁

SCIM

Spinal Cord Independence Measure⬨㧊㞀ᐖ⮬❧ᗘホ౯ἲ⮫ᗋヨ㦂ᐇ᪋ィ⏬᭩࡟㐺ྜࡋࡓᑐ㇟㞟ᅋ

 ཧ⪃㈨ᩱ
࣭ᘬ⏝ᩥ⊩
1) ᪂ᐑᙪຓ. ⬨㧊ᦆയࡢண㜵. ᪥ᮏࣃࣛࣉࣞࢪ࢔་Ꮫ఍㞧ㄅ 13: 48-49, 2000.
2) ᆏ஭ᏹ᪫. ␿Ꮫㄪᰝ. ⥲ྜࣜࣁ 36: 969-972, 2008.
3) Taghva A, Hoh DJ, Lauryssen CL. Advances in the management of spinal cord and spinal column
injuries. Handb Clin Neurol. 109:105-30, 2012.
4) Ditunno JF,Cardenas DD,Formal C,Dalal K. Advances in therehabilitationmanagement of
acutespinalcordinjury.+DQGE&OLQ1HXURO109:18195,2012.
5) Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of multiply
cascade. Acta Neurobiol Exp 71:281-299, 2011.
6) Fawcett JW, Curt A, Steeves JD, Coleman WP, Tuszynski MH, et al. Guidelines for the conduct ofclinical trials for spinal cord injury as developed by the ICCP panel: spontaneous recovery after
spinal cord injury and statistical power needed for therapeutic clinical trials. SpinalCord.
45(3):190-205, 2007.
7) Marino RJ, Ditunno JF Jr, Donovan WH, Maynard FM Jr. Neurologic recovery after traumatic
spinal cord injury: data from the Model Spinal Cord Injury Systems. Arch Phys Med Rehabil. 80:
1391-1396, 1999.
8) Coleman WP, Geisler FH. Injury severity as primary predictor of outcome in acute spinal cord
injury: retrospective results from a large multicenter clinical trial. Spine J 4; 373–378, 2004.
9) Steeves JD, Lammertse D, Curt A, Fawcett JW, Tuszynski MH, et al. International Campaign forCures of Spinal Cord Injury Paralysis. Guidelines for the conduct of clinical trials for spinal cord
injury (SCI) as developed by the ICCP panel: clinical trial outcome measures. Spinal Cord. 45(3):206-21, 2007.
10) Tuszynski MH, Steeves JD, Fawcett JW, Lammertse D, Kalichman M, et al. Guidelines for the13㸫㸫

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conduct of clinical trials for spinal cord injury as developed by the ICCP Panel: clinical trial
inclusion/exclusion criteria and ethics. Spinal Cord. 5(3):222-31, 2007.
11) Krishna V, Andrews H, Varma A, Mintzer J, Kindy MS, Guest J. Spinal cord injury: how can we
improve the classification and quantification of its severity and prognosis? J Neurotrauma.
31(3):215-227, 2014. 15) Bransford RJ, Chapman JR, Skelly AC, VanAlstyne EM. What do wecurrently know about thoracic spinal cord injury recovery and outcomes? A systematic review. J
Neurosurg Spine 17(1 Suppl):52-64, 201212) Bransford RJ, Chapman JR, Skelly AC, VanAlstyne EM. What do we currently know aboutthoracic spinal cord injury recovery and outcomes? A systematic review. J Neurosurg Spine 2012
Sep; 17(1 Suppl): 52-64, 2012
13) Fehlings MG, Vaccaro A, Wilson JR, Singh A, Cadotte DW, et al. Early versus delayed
decompression for traumatic cervical spinal cord injury: Results of the surgical timing in acutespinal cord injury study (STASCIS). PLoS ONE 7(2), 2012.
14) Kawano O, Ueta T, Shiba K, Iwamoto Y. Outcome of decompression surgery for cervical spinal
cord injury without bone and disc injury in patients with spinal cord compression: a multicenterprospective study. Spinal Cord. 48: 548553, 2010.
15) Mazaki T, Ito Y, Sugimoto Y, Koshimune K, Tanaka M, Ozaki T. Does laminoplasty really improveneurological status in patients with cervical spinal cord injury without bone and disc injury? A
prospective study about neurological recovery and early complications. Arch Orthop Trauma Surg.
133:1401-1405, 2013.
16) Newton D, England M, Doll H, Gardner BP. The case of early treatment of dislocations of thecervical spine with cord involvement sustained playing rugby. J Bone Joint Surg Br;93-B:1646–
52, 2011
17) Lammertse D, Tuszynski MH, Steeves JD, Curt A, Fawcett JW, et al. Guidelines for the conductof clinical trials for spinal cord injury as developed by the ICCP panel: clinical trial design. Spinal
Cord.45(3):232-242, 2007.
18) Steeves JD, Lammertse D, Curt A, Fawcett JW, Tuszynski MH, et al. Guidelines for the conductof clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome
measures. Spinal Cord. 45(3):206-21, 2007.
19) Alexander MS, Anderson KD, Biering-Sorensen F, Blight AR, Brannon R, et al. Outcome
measures in spinal cord injury: recent assessments and recommendations for future directions.

14㸫㸫

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Spinal Cord. 47(8):582-91, 2009.
20) Hadley MN, Walters BC, Aarabi BZ, Dhall SS, Gelb DE, et al. Clinical assessment following
acute cervical spinal cord injury. Neurosurgery 72: 40-53, 2013.
21) van Middendorp J J, Hosman AJ, Pouw MH, EM-SCI Study Group, and Van de Meent, H. ASIA
impairment scale conversion in traumatic SCI: is it related with the ability to walk? A descriptive
comparison with functional ambulation outcome measures in 273 patients. Spinal Cord 47: 555–
560, 2009
22) Gündo÷du Í, Akyüz M, Öztürk EA, Çakclí FA. Can spinal cord injury patients show a worsening
in ASIA impairment scale classification despite actually having neurological improvement? The
limitation of ASlA Impairment Scale Classification. Spinal Cord52: 667-670, 2014.
23) Kramer JL, Lammertse DP, Schubert M, Curt A, Steeves JD. Relationship Between Motor
Recovery and Independence After Sensorimotor-Complete Cervical Spinal Cord Injury.
Neurorehabil Neural Repair 26: 1064-71, 2012
24) ManagementofSafetyInformationfromClinicalTrials :ReportofCIOMSWorkingGroupVI,
2005
25)MedDRA®TERMSELECTION:POINTSTOCONSIDER,2013࣭⮫ᗋヨ㦂ࡢᐇ᪋࡟㛵ࡍࡿ ,&+ ࢞࢖ࢻࣛ࢖ࣥ࡟㛵ࡍࡿ୺࡞㏻▱ཬࡧ஦ົ㐃⤡
1. ICHE3㸸ࠕ἞㦂ࡢ⥲ᣓሗ࿌᭩ࡢᵓᡂ࡜ෆᐜ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥ࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 8 ᖺ
5 ᭶ 1 ᪥௜ࡅ⸆ᑂ➨ 335 ྕཌ⏕┬⸆ົᒁᑂᰝㄢ㛗㏻▱㸧ࠊࠕࠕ἞㦂ࡢ⥲ᣓሗ࿌᭩ࡢᵓᡂ
࡜ෆᐜ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࠖ࡟㛵ࡍࡿ㉁␲ᛂ⟅㞟㸦Q&A㸧࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 24 ᖺ 10
᭶ 18 ᪥௜ࡅཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ஦ົ㐃⤡㸧
2. ICHE4㸸ࠕࠕ᪂་⸆ရࡢᢎㄆ࡟ᚲせ࡞⏝㔞̿཯ᛂ㛵ಀࡢ᳨ウࡢࡓࡵࡢᣦ㔪ࠖ࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 6 ᖺ 7 ᭶ 25 ᪥௜ࡅ⸆ᑂ➨ 494 ྕཌ⏕┬⸆ົᒁᑂᰝㄢ㛗㏻▱㸧
3. ICHE5㸸ࠕእᅜ࡛ᐇ᪋ࡉࢀࡓ་⸆ရࡢ⮫ᗋヨ㦂ࢹ࣮ࢱࡢྲྀᢅ࠸࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 10ᖺ 8 ᭶ 11 ᪥௜ࡅ་⸆Ⓨ➨ 739 ྕཌ⏕┬་⸆Ᏻ඲ᒁ㛗㏻▱㸧ࠊࠕࠕእᅜ⮫ᗋࢹ࣮ࢱࢆ
ཷࡅධࢀࡿ㝿࡟⪃៖ࡍ࡭ࡁẸ᪘ⓗせᅉ࡟ࡘ࠸࡚ࡢᣦ㔪ࠖ࡟㛵ࡍࡿ Q&A ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 16 ᖺ 2 ᭶ 25 ᪥௜ࡅཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ஦ົ㐃⤡㸧ࠊࠕࠕእᅜ⮫ᗋࢹ࣮ࢱࢆཷࡅධࢀࡿ㝿࡟⪃៖ࡍ࡭ࡁẸ᪘ⓗせᅉ࡟ࡘ࠸࡚ࡢᣦ㔪ࠖ࡟㛵ࡍࡿ Q&A ࡟ࡘ࠸࡚㸦ࡑࡢ 2㸧ࠖ㸦ᖹᡂ 18 ᖺ 10 ᭶ 5 ᪥௜ࡅཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ஦ົ㐃⤡㸧
4. ICHE7㸸ࠕࠕ㧗㱋⪅࡟౑⏝ࡉࢀࡿ་⸆ရࡢ⮫ᗋホ౯ἲ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࠖ࡟ࡘ࠸
࡚ࠖ㸦ᖹᡂ 5 ᖺ 12 ᭶ 2 ᪥௜ࡅ⸆᪂⸆➨ 104 ྕཌ⏕┬⸆ົᒁ᪂་⸆ရㄢ㛗㏻▱㸧ࠊࠕࠕ㧗㱋⪅࡟౑⏝ࡉࢀࡿ་⸆ရࡢ⮫ᗋホ౯ἲ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࠖ࡟㛵ࡍࡿ㉁␲ᛂ
15㸫㸫

⟅㞟㸦Q&A㸧࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 22 ᖺ 9 ᭶ 17 ᪥௜ཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ஦ົ㐃⤡㸧
5. ICHE8㸸ࠕࠕ⮫ᗋヨ㦂ࡢ୍⯡ᣦ㔪ࠖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 10 ᖺ 4 ᭶ 21 ᪥௜ࡅ་⸆ᑂ➨ 380 ྕཌ⏕┬་⸆Ᏻ඲ᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧
6. ICHE9㸸ࠕࠕ⮫ᗋヨ㦂ࡢࡓࡵࡢ⤫ィⓗཎ๎ࠖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 10 ᖺ 11 ᭶ 30 ᪥௜ࡅ་⸆
ᑂ➨ 1047 ྕཌ⏕┬་⸆Ᏻ඲ᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧
7. ICHE10㸸ࠕ⮫ᗋヨ㦂࡟࠾ࡅࡿᑐ↷⩌ࡢ㑅ᢥ࡜ࡑࢀ࡟㛵㐃ࡍࡿㅖၥ㢟ࠖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ
13 ᖺ 2 ᭶ 27 ᪥௜ࡅ་⸆ᑂⓎ➨ 136 ྕཌ⏕ປാ┬་⸆ᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧
8. ICHE14㸸ࠕ㠀ᢠ୙ᩚ⬦⸆࡟࠾ࡅࡿ QT/QTc 㛫㝸ࡢᘏ㛗࡜ദ୙ᩚ⬦స⏝ࡢ₯ᅾⓗྍ⬟ᛶ࡟㛵ࡍࡿ⮫ᗋⓗホ౯࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 21 ᖺ 10 ᭶ 23 ᪥௜ࡅ⸆㣗ᑂᰝⓎ 1023 ➨㸯ྕཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧ࠊࠕࠕ㠀ᢠ୙ᩚ⬦⸆࡟࠾ࡅࡿ QT/QTc 㛫㝸ࡢᘏ㛗࡜ദ୙ᩚ⬦స⏝ࡢ₯ᅾⓗྍ⬟ᛶ࡟㛵ࡍࡿ⮫ᗋⓗホ౯ࠖ࡟㛵ࡍࡿ Q&A ࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 29 ᖺ 5 ᭶ 23 ᪥௜ࡅཌ⏕ປാ┬་⸆࣭⏕ά⾨⏕ᒁ་⸆ရᑂᰝ⟶⌮ㄢ஦ົ㐃⤡㸧
9. ICHE17㸸ࠕᅜ㝿ඹྠ἞㦂ࡢィ⏬ཬࡧࢹࢨ࢖ࣥ࡟㛵ࡍࡿ୍⯡ཎ๎࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥ
࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 3 0 ᖺ 6 ᭶ 1 2 ᪥௜ࡅ⸆⏕⸆ᑂⓎ 0612 ➨ 1 ྕཌ⏕ປാ┬་⸆࣭⏕ά⾨⏕ᒁ་⸆ရᑂᰝ⟶⌮ㄢ㛗㏻▱㸧
10. ICHM3㸸ࠕࠕ་⸆ရࡢ⮫ᗋヨ㦂ཬࡧ〇㐀㈍኎ᢎㄆ⏦ㄳࡢࡓࡵࡢ㠀⮫ᗋᏳ඲ᛶヨ㦂ࡢᐇ᪋࡟ࡘ࠸࡚ࡢ࢞࢖ࢲࣥࢫࠖ࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 22 ᖺ 2 ᭶ 19 ᪥௜ࡅ⸆㣗ᑂᰝⓎ 0210 ➨ 4ྕཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧ࠊࠕࠕ་⸆ရࡢ⮫ᗋヨ㦂ཬࡧ〇㐀㈍኎ᢎㄆ
⏦ㄳࡢࡓࡵࡢ㠀⮫ᗋᏳ඲ᛶヨ㦂ࡢᐇ᪋࡟ࡘ࠸࡚ࡢ࢞࢖ࢲࣥࢫࠖ࡟㛵ࡍࡿ㉁␲ᛂ⟅㞟
㸦Q&A㸧࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 24 ᖺ 8 ᭶ 16 ᪥௜ࡅཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ஦ົ㐃⤡㸧࣭ࡑࡢ௚⮫ᗋヨ㦂ࡢᐇ᪋࡟࠶ࡓࡾཧ↷ࡍ࡭ࡁ୺࡞㏻▱ཬࡧ஦ົ㐃⤡
1. ࠕ་⸆ရࡢ⮫ᗋ⸆≀ືែヨ㦂࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 13 ᖺ 6 ᭶ 1 ᪥௜ࡅ་⸆ᑂⓎ➨ 796 ྕཌ⏕ປാ┬་⸆ᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧 
2. ࠕࠕ་⸆ရ㛤Ⓨ࡜㐺ṇ࡞᝟ሗᥦ౪ࡢࡓࡵࡢ⸆≀┦஫స⏝࢞࢖ࢻࣛ࢖ࣥࠖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 30 ᖺ 7 ᭶ 23 ᪥௜ࡅ⸆⏕⸆ᑂⓎ 0723 ➨ 4 ྕཌ⏕ປാ┬་⸆࣭⏕ά⾨⏕ᒁ་⸆ရᑂᰝ⟶⌮ㄢ㛗㏻▱㸧
3. ࠕᅜ㝿ඹྠ἞㦂࡟㛵ࡍࡿᇶᮏⓗ⪃࠼᪉࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 19 ᖺ 9 ᭶ 28 ᪥௜ࡅ⸆㣗ᑂᰝⓎ➨ 0928010 ྕཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧 16㸫㸫⸆⏕ᶵᑂⓎ㸮㸴㸰㸵➨㸯ྕ௧ ࿴ ඖ ᖺ 㸴 ᭶ 㸰 㸵 ᪥ྛ㒔㐨ᗓ┴⾨⏕୺⟶㒊㸦ᒁ㸧㛗Ẋཌ⏕ປാ┬་⸆࣭⏕ά⾨⏕ᒁ་⒪ᶵჾᑂᰝ⟶⌮ㄢ㛗
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ࣄࢺ⣽⬊ຍᕤ〇ရࡢᮍศ໬ከ⬟ᛶᖿ⣽⬊࣭ᙧ㉁㌿᥮⣽⬊᳨ฟヨ㦂ࠊ㐀⭘⒆ᛶヨ㦂ཬࡧ㑇ఏⓗᏳᐃᛶホ౯࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥ࡟ࡘ࠸࡚
ࣄࢺ⣽⬊ຍᕤ〇ရ୰࡟ΰᅾࡍࡿᮍศ໬ከ⬟ᛶᖿ⣽⬊ཬࡧᙧ㉁㌿᥮⣽⬊࡟ࡘ࠸࡚ࠊ௦⾲ⓗ᳨ฟヨ㦂౛ཬࡧ≉ᐃࡢࣄࢺ⣽⬊ຍᕤ〇ရࡢရ㉁࣭Ᏻ඲ᛶホ౯ࡢࡓࡵ࡟ᐇ᪋ࡍࡿヨ㦂ࢆ㑅ᢥࡍࡿ㝿࡟␃ពࡍ࡭ࡁ஦㡯ࢆ♧ࡍ࢞࢖ࢻࣛ࢖ࣥࢆࠊู⣬ࡢ࡜࠾ࡾసᡂࡋࡲࡋࡓࡢ࡛ࠊ㈗⟶ୗ㛵ಀᴗ⪅➼࡟ᑐࡋ࿘▱᪉ᚚ㓄៖㢪࠸ࡲࡍࠋ
࡞࠾ࠊᮏ࢞࢖ࢻࣛ࢖ࣥࡣࠊ⌧᫬Ⅼ࡟࠾ࡅࡿ⛉Ꮫⓗ▱ぢ࡟ᇶ࡙ࡃᇶᮏⓗ⪃࠼᪉ࢆࡲ࡜ࡵࡓࡶࡢ࡛࠶ࡾࠊᏛၥୖࡢ㐍Ṍ➼ࢆ཯ᫎࡋࡓྜ⌮ⓗ᰿ᣐ࡟ᇶ࡙࠸ࡓࡶࡢ
࡛࠶ࢀࡤࠊᚲࡎࡋࡶࡇࡇ࡟♧ࡋࡓ᪉ἲࢆᅛᏲࡍࡿࡼ࠺ồࡵࡿࡶࡢ࡛ࡣ࠶ࡾࡲࡏ
ࢇࠋ㸫㸫ูῧࣄࢺ⣽⬊ຍᕤ〇ရࡢᮍศ໬ከ⬟ᛶᖿ⣽⬊࣭ᙧ㉁㌿᥮⣽⬊᳨ฟヨ㦂ࠊ㐀⭘⒆ᛶヨ㦂ཬࡧ㑇ఏⓗᏳᐃᛶホ౯࡟㛵ࡍࡿ␃ពⅬ
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㸯㸬ࡣࡌࡵ࡟

㸰㸬ᮏᩥ᭩ࡢ఩⨨࡙ࡅ㸱㸬⏝ㄒࡢᐃ⩏㸲㸬୍⯡ⓗ␃ពⅬ㸳㸬ࣄࢺ (6L36 ⣽⬊ຍᕤ〇ရࡢࡓࡵࡢ㐀⭘⒆ᛶ㛵㐃ヨ㦂ཎᩱ࣭ཎᮦᩱࡢရ㉁≉ᛶホ౯࣭ရ㉁⟶⌮ࡢࡓࡵࡢ㐀⭘⒆ᛶヨ㦂୰㛫〇ရཪࡣ᭱⤊〇ရࡢ㐀⭘⒆ᛶ⣽⬊ࡢΰᅾࢆホ౯ࡍࡿࡓࡵࡢヨ㦂୰㛫〇ရ࣭᭱⤊〇ရࡢᮍศ໬ከ⬟ᛶᖿ⣽⬊᳨ฟヨ㦂LQYLWUR ヨ㦂LQYLYR ヨ㦂୰㛫〇ရ࣭᭱⤊〇ရࡢᙧ㉁㌿᥮⣽⬊᳨ฟヨ㦂LQYLWUR ヨ㦂LQYLYR ヨ㦂᭱⤊〇ရ⣽⬊ࡢࣄࢺ࡟࠾ࡅࡿ⏕╔㒊఩࡛ࡢ⭘⒆ᙧᡂ⬟ࢆホ౯ࡍࡿࡓࡵࡢヨ㦂ヨ㦂ື≀ࡢ㑅ᢥᑐ↷⣽⬊ࡢ㑅ᢥヨ㦂ື≀ࡢᩘ࡜ᛶู

ヨ㦂᳨యࡢᢞ୚㒊఩࡜᳨య୰ࡢ⣽⬊ᩘཬࡧ᳨యࡢᙧែ

ほᐹᮇ㛫ᢞ୚㒊఩ࡢほᐹ⑓⌮Ꮫⓗホ౯⤖ᯝࡢゎ㔘㸴㸬ࣄࢺయ⣽⬊㸭యᛶᖿ⣽⬊ຍᕤ〇ရࡢࡓࡵࡢ㐀⭘⒆ᛶ㛵㐃ヨ㦂ཎᩱ࣭ཎᮦᩱࡢရ㉁≉ᛶホ౯࣭ရ㉁⟶⌮ࡢࡓࡵࡢ㐀⭘⒆ᛶヨ㦂᭱⤊〇ရࡢࡓࡵࡢ㐀⭘⒆ᛶ㛵㐃ヨ㦂ࡢ␃ពⅬ㸵㸬㑇ఏⓗᏳᐃᛶ࡟㛵ࡍࡿ୍⯡ⓗ␃ពⅬ

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⾲㸯 ΰᅾࡍࡿᮍศ໬ (6L36 ⣽⬊ࡢ᳨ฟἲࡢヲ⣽⾲㸰 ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊ࡢ᳨ฟἲࡢヲ⣽ཧ⪃᝟ሗ㸦ྛ✀ヨ㦂ἲࣉࣟࢺࢥ࣮ࣝ㸧㸫㸫

㸯㸬ࡣࡌࡵ࡟෌⏕་⒪➼〇ရ㸦ࠕ་⸆ရࠊ་⒪ᶵჾ➼ࡢရ㉁ࠊ᭷ຠᛶཬࡧᏳ඲ᛶࡢ☜ಖ➼࡟㛵ࡍࡿἲᚊࠖ
㸦᫛࿴ 35 ᖺἲᚊ➨ 145 ྕ㸧➨ 2 ᮲➨ 9 㡯࡟つᐃࡍࡿࠕ෌⏕་⒪➼〇ရࠖࢆ࠸࠺ࠋ௨ୗྠࡌࠋ
㸧ࡢ࠺ࡕࠊࣄࢺ⣽⬊ຍᕤ〇ရࡢရ㉁ཬࡧᏳ඲ᛶࢆ☜ಖࡍࡿࡓࡵࡢᇶᮏⓗ࡞ᢏ⾡せ௳ࡣࠊࠕࣄࢺ㸦⮬ᕫ㸧⏤᮶⣽⬊ࡸ⤌⧊ࢆຍᕤࡋࡓ་⸆ရཪࡣ་⒪ᶵჾࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 20 ᖺ㸰᭶㸶᪥௜ࡅ⸆㣗Ⓨ➨ 0208003 ྕཌ⏕ປാ┬་⸆㣗ရᒁ㛗㏻▱ࠋ௨ୗ㺀ࣄࢺ㸦⮬ᕫ㸧⏤᮶⣽⬊࣭⤌⧊ຍᕤ་⸆ရ➼ࡢᣦ㔪㺁࡜࠸࠺ࠋ㸧ཬࡧࠕࣄࢺ㸦ྠ✀㸧⏤᮶⣽⬊ࡸ⤌⧊ࢆຍᕤࡋࡓ་⸆ရཪࡣ་⒪ᶵჾࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 20 ᖺ㸷᭶ 12 ᪥௜ࡅ⸆㣗Ⓨ➨ 0912006 ྕཌ⏕ປാ┬་⸆㣗ရᒁ㛗㏻▱ࠋ௨ୗ㺀ࣄࢺ㸦ྠ✀㸧⏤᮶⣽⬊࣭⤌⧊ຍᕤ་⸆ရ➼ࡢᣦ㔪㺁࡜࠸࠺ࠋ㸧࡟ᐃࡵࡽࢀ࡚࠸ࡿ࡜ࡇࢁ࡛࠶ࡿࠋࡲࡓࠊࣄࢺ⣽⬊ຍᕤ〇ရࡢ୰࡛ࡶࠊ
ࣄࢺᖿ⣽⬊ຍᕤ〇ရࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟ࡘ࠸࡚ࡣࠊࠕࣄࢺ㸦⮬ᕫ㸧యᛶᖿ⣽⬊ຍᕤ་⸆ရ➼ࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 24 ᖺ㸷᭶㸵᪥௜ࡅ⸆㣗Ⓨ➨ 0907 ➨㸰ྕཌ⏕ປാ┬་⸆㣗ရᒁ㛗㏻▱㸧ࠊࠕࣄࢺ㸦ྠ✀㸧యᛶᖿ⣽⬊ຍᕤ་⸆ရ➼ࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 24 ᖺ㸷᭶㸵᪥௜ࡅ⸆㣗Ⓨ➨ 0907 ➨㸱ྕཌ⏕ປാ┬་⸆㣗ရᒁ㛗㏻▱㸧ࠊࠕࣄࢺ㸦⮬ᕫ㸧iPS㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟ࡘ࠸࡚ࠖ㸦ᖹᡂ 24 ᖺ㸷᭶㸵᪥௜ࡅ⸆㣗Ⓨ➨ 0907 ➨㸲ྕཌ⏕ປാ┬་⸆㣗ရᒁ㛗㏻▱㸧ࠊࠕࣄࢺ㸦ྠ✀㸧iPS㸦ᵝ㸧⣽⬊ຍᕤ་⸆ရ➼ࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 24 ᖺ㸷᭶㸵᪥௜ࡅ⸆㣗Ⓨ➨ 0907
➨㸳ྕཌ⏕ປാ┬་⸆㣗ရᒁ㛗㏻▱㸧ཬࡧࠕࣄࢺ ES ⣽⬊ຍᕤ་⸆ရ➼ࡢရ㉁ཬࡧᏳ඲ᛶࡢ
☜ಖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 24 ᖺ㸷᭶㸵᪥௜ࡅ⸆㣗Ⓨ➨ 0907 ➨㸴ྕཌ⏕ປാ┬་⸆㣗ရᒁ㛗㏻▱㸧㸦௨ୗ㺀ࣄࢺᖿ⣽⬊ຍᕤ་⸆ရ➼ 5 ᣦ㔪㺁࡜⥲⛠ࡍࡿࠋ㸧࡟ࡶᐃࡵࡽࢀ࡚࠸ࡿ࡜ࡇࢁ࡛࠶ࡿࠋ
ࣄࢺ⣽⬊ຍᕤ〇ရ࡟≉᭷ࡢᏳ඲ᛶ㛵㐃ࣜࢫࢡ࡜ࡋ࡚ࡣࠊ〇ရ୰࡟ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊࡟㉳ᅉࡍࡿ⭘⒆ᙧᡂࡢࣜࢫࢡࡀ࠶ࡿࠋࡲࡓࠊࣄࢺ⬇ᛶᖿ⣽⬊ຍᕤ〇ရ㸦௨ୗࠕࣄࢺ ES ⣽⬊ຍᕤ〇ရࠖ࡜࠸࠺ࠋ
㸧ࡸࣄࢺேᕤከ⬟ᛶᖿ⣽⬊ຍᕤ〇ရ㸦௨ୗࠕࣄࢺ iPS ⣽⬊ຍᕤ〇ရࠖ࡜࠸࠺ࠋ㸧ࡢࡼ࠺࡟ࢸࣛࢺ࣮࣐ᙧᡂ⬟ࢆᅛ᭷ࡢᛶ㉁࡜ࡍࡿࣄࢺከ⬟ᛶᖿ⣽⬊ࢆཎᩱ࡜ࡍࡿሙྜ
࡟ࡣࠊ᭱⤊〇ရ࡟ṧᏑࡍࡿᮍศ໬࡞ከ⬟ᛶᖿ⣽⬊࡟㉳ᅉࡍࡿ⭘⒆ᙧᡂࡢࣜࢫࢡࡶ࠶ࡿࠋࡍ࡞
ࢃࡕࠊࣄࢺ⣽⬊ຍᕤ〇ရ୰࡟ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊ཬࡧᮍศ໬࡞ከ⬟ᛶᖿ⣽⬊➼ࡢ㐀⭘⒆ᛶ⣽⬊ࡣࣁࢨ࣮ࢻ࡛࠶ࡾࠊࡑࡢᏑᅾ㔞ཬࡧ✀㢮ࡢ᝟ሗࢆᢕᥱࡍࡿࡇ࡜ࡣࠊࣄࢺ⣽⬊ຍᕤ〇ရ
ࡢရ㉁ཬࡧᏳ඲ᛶࡢ☜ಖ࡟࠾࠸࡚㔜せ࡛࠶ࡿࠋᮏᩥ᭩ࡣࠊࣄࢺ⣽⬊ຍᕤ〇ရࡢရ㉁ཬࡧᏳ඲
ᛶࢆ㠀⮫ᗋⓗ࡟ホ౯ࡍࡿ㝿࡟ཧ⪃࡜ࡍ࡭ࡁ஦㡯ཬࡧ␃ពⅬࡢ࠺ࡕࠊ≉࡟ࣄࢺ⣽⬊ຍᕤ〇ရ୰࡟ΰᅾࡍࡿᮍศ໬ከ⬟ᛶᖿ⣽⬊ཬࡧᙧ㉁㌿᥮⣽⬊࡟ࡘ࠸࡚ࠊࡑࡢ௦⾲ⓗ᳨ฟヨ㦂౛ࢆ♧ࡍ࡜ྠ᫬࡟ࠊࡇࢀࡽࡢヨ㦂ࡢ୰࠿ࡽࠊ≉ᐃࡢࣄࢺ⣽⬊ຍᕤ〇ရࡢရ㉁࣭Ᏻ඲ᛶホ౯ࡢࡓࡵ࡟
ᐇ᪋ࡍࡿヨ㦂ࢆ㑅ᢥࡍࡿ㝿࡟␃ពࡍ࡭ࡁ஦㡯ࢆ♧ࡍࡶࡢ࡛࠶ࡿࠋ
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㸰㸬ᮏᩥ᭩ࡢ఩⨨࡙ࡅᮏᩥ᭩ࡣࠊᢏ⾡㛤Ⓨࡢⴭࡋ࠸ከ✀ከᵝ࡞ࣄࢺ⣽⬊ຍᕤ〇ရ୰࡟ΰᅾࡍࡿྍ⬟ᛶࡀ࠶ࡿ㐀⭘⒆ᛶ⣽⬊ࡢ᳨ฟࢆᑐ㇟࡜ࡍࡿࡶࡢ࡛࠶ࡿࠋࡲࡓࠊ᳨ฟヨ㦂ࡑࡢࡶࡢࡢ㛤Ⓨࡸᢏ⾡㠉᪂ࡶ᪥㐍᭶Ṍ࡛࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊ␃ពࡍ࡭ࡁ஦㡯ࢆ⥙⨶ⓗ࡟♧ࡋࡓࡶࡢ࡛ࡣ࡞ࡃࠊ⌧᫬Ⅼ࡛⪃࠼ࡽࢀࡿⅬ࡟ࡘ࠸࡚ྍ⬟࡞㝈ࡾ♧ࡋ࡚࠸ࡿ࡟㐣ࡂࡎࠊ௒ᚋࡢ᭦࡞ࡿᢏ⾡㠉᪂ࡸ▱ぢࡢ㞟✚➼ࢆ
㋃ࡲ࠼ᨵゞࡉࢀࡿࡶࡢ࡛࠶ࡾࠊࡑࡢࡲࡲ〇㐀㈍኎ᢎㄆ⏦ㄳ࡟࠾࠸࡚㐺⏝ࡉࢀࡿ࡭ࡁ࡜ࡢᣊ
᮰ຊࢆ᭷ࡍࡿࡶࡢ࡛ࡣ࡞࠸ࠋࡲࡓࠊᮏᩥ᭩ࡣྛヨ㦂ࡢ≉ᚩ࣭ᛶ⬟ࢆᩚ⌮ࡋࡓࡶࡢ࡛࠶ࡗ࡚ࠊ
㛤Ⓨẁ㝵ࡢ࡝ࡢࢫࢸ࣮ࢪ࡟㐺⏝ࡍ࡭ࡁ࠿ࢆ᫂♧ࡍࡿࡶࡢ࡛ࡣ࡞࠸ࠋ〇ရࡢホ౯࡟ᙜࡓࡗ࡚ࡣࠊಶูࡢ〇ရࡢ≉ᛶࢆ༑ศ⌮ゎࡋࡓୖ࡛ࠊ⛉Ꮫⓗ࡞ྜ⌮ᛶ࣭ጇᙜᛶࢆࡶࡗ࡚ᰂ㌾࡟ᑐᛂࡍࡿࡇ࡜ࡀᚲせ࡛࠶ࡿࠋᮏᩥ᭩࡛ᥦ♧ࡉࢀࡓヨ㦂ἲࡸࡑࡢヲ⣽࡟ࡘ࠸࡚ࡶࠊヨ㦂ࡢ┠ⓗ࡟㐺࠺ࡼ࠺୍㒊ᨵኚࡍࡿࡇ࡜ࡸࠊ┬␎ࡍࡿࡇ࡜ࡶࠊࡑࡢ⛉Ꮫⓗ࡞ྜ⌮ᛶ࣭ጇᙜᛶࡀ♧ࡉࢀࢀࡤࡴࡋࢁዡບࡉࢀࡿࠋ࡞࠾ࠊᮏᩥ᭩ࡢ࡯࠿ࠊᅜෆእࡢ௚ࡢ㛵㐃࢞࢖ࢻࣛ࢖
ࣥࢆཧ⪃࡟ࡍࡿࡇ࡜ࡶ⪃៖ࡍ࡭ࡁ࡛࠶ࡿࠋ
㸱㸬⏝ㄒࡢᐃ⩏ᮏᩥ᭩࡟࠾ࡅࡿ⏝ㄒࡢᐃ⩏ࡣࠊࣄࢺ㸦⮬ᕫ㸧⏤᮶⣽⬊࣭⤌⧊ຍᕤ་⸆ရ➼ࡢᣦ㔪ࠊࣄࢺ㸦ྠ✀㸧⏤᮶⣽⬊࣭⤌⧊ຍᕤ་⸆ရ➼ࡢᣦ㔪ࠊࣄࢺᖿ⣽⬊ຍᕤ་⸆ရ➼ 5 ᣦ㔪ࡢᐃ⩏࡟ࡼࡿ࡯࠿ࠊ௨ୗࡢ࡜࠾ࡾ࡜ࡍࡿࠋ
1) 㐀⭘⒆ᛶ㸦tumorigenicity㸧㸸ື≀࡟⛣᳜ࡉࢀࡓ⣽⬊㞟ᅋࡀቑṪࡍࡿࡇ࡜࡟ࡼࡾࠊᝏᛶཪ
ࡣⰋᛶࡢ⭘⒆ࢆᙧᡂࡍࡿ⬟ຊࡢࡇ࡜ࠋ⏕⌮άᛶ≀㉁ཪࡣ໬Ꮫ≀㉁ࡀ⣽⬊ࢆ୙Ṛ໬ࡋ࡚ᝏᛶཪࡣⰋᛶࡢ⭘⒆ࢆㄏⓎࡍࡿ⬟ຊ㸦⭘⒆ཎᛶࠊoncogenicity㸧ࡸࠊ⏕⌮άᛶ≀㉁ཪࡣ
໬Ꮫ≀㉁ࡀ⣽⬊ࢆ୙Ṛ໬ࡋ࡚ᝏᛶ⭘⒆ࢆㄏⓎࡍࡿ⬟ຊ㸦ࡀࢇཎᛶࠊcarcinogenicity㸧࡜ࡣ༊ูࡉࢀࡿࠋ࡞࠾ࠊᮏᩥ᭩࡛ࡣࠊES/iPS ⣽⬊㸦〇ရ୰࡛ࡣᮍศ໬ ES/iPS ⣽⬊࡜⛠ࡍࡿ㸧ࡸ⭘⒆ࢆᙧᡂࡍࡿ࠾ࡑࢀࡢ࠶ࡿᙧ㉁㌿᥮⣽⬊ࡣື≀ヨ㦂࡛ࡢᐇドࡢ᭷↓࡟࠿࠿ࢃࡽࡎ㐀⭘⒆ᛶ⣽⬊࡜ࡋ࡚ྲྀࡾᢅ࠺ࠋ
2) ⣽⬊ᇶᮦ㸸ᚤ⏕≀⣽⬊ཪࡣࣄࢺⱝࡋࡃࡣື≀⏤᮶ࡢ⣽⬊࡛ࠊࣄࢺࢆᑐ㇟࡟ in vivo ཪࡣ
ex vivo ࡛ᢞ୚ࡉࢀࡿ⏕≀〇๣㸦෌⏕་⒪➼〇ရࢆྵࡴ㸧ࢆ⏕⏘ࡍࡿୖ࡛ᚲせ࡞⬟ຊࢆ᭷ࡍࡿࡶࡢ㸦ࠕࠕ⏕≀⸆ရ㸦ࣂ࢖࢜ࢸࢡࣀࣟࢪ࣮ᛂ⏝་⸆ရ⏕≀㉳※⏤᮶་⸆ရ㸧〇㐀⏝⣽⬊ᇶᮦࡢ⏤᮶ࠊㄪ〇ཬࡧ≉ᛶゎᯒࠖ࡟ࡘ࠸࡚ࠖ
㸦ᖹᡂ 12 ᖺ㸵᭶ 14 ᪥௜ࡅ་⸆ᑂ
➨ 873 ྕཌ⏕┬་⸆Ᏻ඲ᒁᑂᰝ⟶⌮ㄢ㛗㏻▱㸧ཧ↷㸧ࠋ3) ࢭ࣭ࣝࣂࣥࢡ㸸ᆒ୍࡞⤌ᡂࡢෆᐜ≀ࢆࡑࢀࡒࢀ࡟ྵࡴ┦ᙜᩘࡢᐜჾࢆ㞟ࡵࡓ≧ែ࡛ࠊ୍ᐃࡢ᮲௳ୗ࡛ಖᏑࡋ࡚࠸ࡿࡶࡢࠋಶࠎࡢᐜჾ࡟ࡣࠊ༢୍ࡢ⣽⬊ࣉ࣮ࣝ࠿ࡽศὀࡉࢀ
ࡓ⣽⬊ࡀྵࡲࢀ࡚࠸ࡿ㸦ࠕࠕ⏕≀⸆ရ㸦ࣂ࢖࢜ࢸࢡࣀࣟࢪ࣮ᛂ⏝་⸆ရ⏕≀㉳※⏤᮶་⸆ရ㸧〇㐀⏝⣽⬊ᇶᮦࡢ⏤᮶ࠊㄪ〇ཬࡧ≉ᛶゎᯒࠖ࡟ࡘ࠸࡚ࠖཧ↷㸧ࠋ4) ཎᮦᩱ㸸་⸆ရ➼ࡢ〇㐀࡟౑⏝ࡍࡿཎᩱཪࡣᮦᩱࡢ⏤᮶࡜࡞ࡿࡶࡢ㸦ࠕ⏕≀⏤᮶ཎᩱᇶ‽ࠖ㸦ᖹᡂ 26 ᖺཌ⏕ປാ┬࿌♧➨ 375 ྕ㸧ཧ↷㸧
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㸫㸫5) ୰㛫〇ရ㸸〇㐀ࡢ୰㛫ᕤ⛬࡛㐀ࡽࢀࡓࡶࡢ࡛࠶ࡗ࡚ࠊ௨ᚋࡢ〇㐀ᕤ⛬ࢆ⤒ࡿࡇ࡜࡟ࡼࡗ࡚〇ရ࡜࡞ࡿࡶࡢ㸦ࠕ෌⏕་⒪➼〇ရࡢ〇㐀⟶⌮ཬࡧရ㉁⟶⌮ࡢᇶ‽࡟㛵ࡍࡿ┬௧ࠖ㸦ᖹᡂ 26 ᖺཌ⏕ປാ┬௧➨ 93 ྕࠋ௨ୗࠕGCTP ┬௧ࠖ࡜࠸࠺ࠋ㸧ཧ↷㸧ࠋ6) ⭘⒆㸸⣽⬊ࡀ⏕యෆࡢไᚚ࡟཯ࡋ࡚⮬ᚊⓗ࡟㐣๫࡟ቑṪࡍࡿࡇ࡜࡟ࡼࡗ࡚࡛ࡁࡿ⤌⧊ࠋࠕᝏᛶ⭘⒆ࠖཪࡣࠕⰋᛶ⭘⒆ࠖ࡟ศࡅࡽࢀࡿࠋ
7) ࢸࣛࢺ࣮࣐㸦ወᙧ⭘㸧㸸 㸰⬇ⴥᛶᡂศཪࡣ㸱⬇ⴥᛶᡂศࢆ᭷ࡍࡿ⬇⣽⬊ᛶ⭘⒆ࠋ
ࠕᡂ⇍ወᙧ⭘ࠖ࡜ࠕᮍ⇍ወᙧ⭘ࠖࡀ࠶ࡿࠋ
8) ᝏᛶ⭘⒆㸸⭘⒆ࡢ୰࡛ࡶ≉࡟ᾐ₶ᛶࢆ᭷ࡋࠊ㐲㝸㒊࡬㌿⛣ࡍࡿ࡞࡝ᝏᛶࢆ♧ࡍࡶࡢࢆᣦࡍࠋ9) ࡀࢇ㸸ᖹ௬ྡࡢࠕࡀࢇࠖࡣࠊ
ࠕ⒴ࠖࠊ
ࠕ⫗⭘ࠖཬࡧࠕⓑ⾑⑓ࠖ࡞࡝ࡢ⾑ᾮᝏᛶ⭘⒆ࡶྵࡵ
ࡓᗈ⩏ࡢᝏᛶ⭘⒆ࢆᣦࡍࠋ₎Ꮠ࡛⾲グࡍࡿࠕ⒴ࠖࡣࠊᝏᛶ⭘⒆ࡢ࡞࠿࡛ࡶ≉࡟ୖ⓶⏤᮶ࡢࠕ⒴⭘㸦ୖ⓶⭘㸧ࠖࡢࡇ࡜ࢆᣦࡍࠋ
ࠕ⫗⭘ࠖ࡜ࡣ㠀ୖ⓶ᛶࡢ⤖ྜ⤌⧊ࠊ➽ࠊෆ⓶⣽⬊➼࡟⏤᮶ࡍࡿᝏᛶ⭘⒆࡛࠶ࡿࠋ
10) ⭘⒗㸸Ⓨ⏕ཎᅉ࡟㛵ࢃࡽࡎࠊయ⾲ࡸయෆ࡛☜ㄆࡉࢀࡓఱࡽ࠿ࡢሢࠋ࠸ࢃࡺࡿࠕࡋࡇࡾࠖ
ࡸࠕࡇࡪࠖࢆᣦࡍࠋ⭘⒗࡜⭘⒆ࡢ㐪࠸࡟ࡘ࠸࡚ࡣࠊ⭘⒗ࡣ⮋⒆࡞࡝ࡶྵࡴࠕᙧែ࡛ࠖ࠶ࡾࠊ⭘⒆ࡣ⣽⬊ࡀቑṪࡋࡓࠕ⑓ែ࡛ࠖ࠶ࡿࠋ
11) ᙧ㉁㌿᥮⣽⬊㸸୙Ṛ໬ࡸᝏᛶ໬࡞࡝ࠊ㐀⭘⒆ᛶ࡟㛵㐃ࡋࡓᙧ㉁㌿᥮ࡀ⏕ࡌࡓ⣽⬊ࢆᣦࡍࠋ12) 〇ရ⣽⬊㸸〇ရ࡟ྵࡲࢀࡿ⣽⬊13) ᭱⤊〇ရ⣽⬊㸸᭱⤊〇ရ࡟ྵࡲࢀࡿ⣽⬊14) ࣁࢨ࣮ࢻ㸸༴ᐖࡢ₯ᅾⓗ࡞ཎᅉࠋ༴ᐖࡣࠊ೺ᗣ࡬ࡢ⿕ᐖࢆᣦࡍࠋ
㸦
ࠕရ㉁ࣜࢫࢡ࣐ࢿࢪ
࣓ࣥࢺ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࠖ
㸦ᖹᡂ 18 ᖺ 9 ᭶ 1 ᪥௜ࡅ⸆㣗ᑂᰝⓎ➨ 0901004 ྕཬࡧ⸆㣗┘㯞Ⓨ➨ 0901005 ྕཌ⏕ປാ┬་⸆㣗ရᒁᑂᰝ⟶⌮ㄢ㛗ཬࡧ┘どᣦᑟ࣭㯞⸆ᑐ⟇ㄢ㛗㐃ྡ㏻▱㸧ཧ↷㸧15) ࣜࢫࢡ㸸༴ᐖࡢⓎ⏕ࡢ☜⋡࡜ࡑࢀࡀⓎ⏕ࡋࡓ࡜ࡁࡢ㔜኱ᛶࡢ⤌ࡳྜࢃࡏࠋ㔜኱ᛶࡣࠊࣁࢨ࣮ࢻ࠿ࡽ⏕ࡌ࠺ࡿ⤖ᯝࡢ኱ࡁࡉࢆᣦࡍࠋ
㸦ࠕရ㉁ࣜࢫࢡ࣐ࢿࢪ࣓ࣥࢺ࡟㛵ࡍࡿ࢞࢖ࢻࣛ࢖ࣥࠖཧ↷㸧㸲㸬୍⯡ⓗ␃ពⅬࣄࢺ⣽⬊ຍᕤ〇ရࡢฟⓎཎᩱࡢ✀㢮ࡣࠊయ⣽⬊ࠊయᛶᖿ⣽⬊ࠊES ⣽⬊ࠊiPS ⣽⬊࡞࡝ࠊከᒱ࡟ࢃࡓࡿࠋࡉࡽ࡟ࠊฟⓎཎᩱ⣽⬊ࡢ⏤᮶࡟ࡘ࠸࡚ࡣࠊ⮬ᕫཪࡣྠ✀ࠊྠ✀ࡢ࠺ࡕ࡛ࡣ HLA࣍ࣔ᥋ྜᆺཪࡣࡑࢀ௨እ࡞࡝ࠊᵝࠎ࡞ศ㢮ࡀ᝿ᐃࡉࢀࡿࠋࣄࢺ⣽⬊ຍᕤ〇ရࡣᵓ㐀ཪࡣ๣ᙧ㸦౛㸸⣽⬊ᠱ⃮ᾮࠊ⣽⬊ࢩ࣮ࢺ➼㸧ࡶከᵝ࡛࠶ࡾࠊࡑࡢ⮫ᗋ㐺⏝࡟㝿ࡋ࡚ᚲせ࡞⣽⬊ᩘࡶ〇ရࡈ࡜࡟␗࡞ࡿࠋࡑࡢୖࠊ㐺⏝ࡢ⤒㊰ࠊ㐺⏝㒊఩ࠊච␿ᢚไ๣ࡢ౑⏝ࡢ᭷↓ࠊᝈ⪅ࡢ⑓≧ࡢ⥭ᛴᛶ➼࡟ࡘ࠸࡚ࡶࠊᵝࠎ࡞ࢣ࣮ࢫࡀ᝿ᐃࡉࢀࡿࠋࡋࡓࡀࡗ࡚ࠊಶู〇ရ࡟࠾ࡅࡿ㐀⭘⒆ᛶ
ࡢࣜࢫࢡホ౯࡜ࣜࢫࢡ⟶⌮࡟࠾࠸࡚ࡣࠊྛヨ㦂ἲࡢ⬟ຊ࡜㝈⏺ࢆ⛉Ꮫⓗ࡟⌮ゎࡋࡓୖ࡛ࠊ⥲㸫㸫ྜⓗ࡞⪃ᐹࢆ⾜࠺ࡇ࡜ࠋ㸳㸬ࣄࢺ (6L36 ⣽⬊ຍᕤ〇ရࡢࡓࡵࡢ㐀⭘⒆ᛶ㛵㐃ヨ㦂ࣄࢺ⬇ᛶᖿ⣽⬊ຍᕤ〇ရཪࡣࣄࢺேᕤከ⬟ᛶ⣽⬊ຍᕤ〇ရ㸦ࣄࢺ ES/iPS ⣽⬊ຍᕤ〇ရ㸧ࡢ〇㐀࡟࠾ࡅࡿ㐀⭘⒆ᛶ㛵㐃ヨ㦂࡟ࡣࠊ┠ⓗู࡟ࠊձཎᩱ࣭ཎᮦᩱࡢရ㉁≉ᛶホ౯࣭ရ㉁⟶⌮ࡢࡓࡵࡢ㐀⭘⒆ᛶヨ㦂ࠊղ୰㛫〇ရཪࡣ᭱⤊〇ရࡢ㐀⭘⒆ᛶ⣽⬊ࡢΰᅾࢆホ౯ࡍࡿࡓࡵ
ࡢヨ㦂ࠊճ᭱⤊〇ရ⣽⬊ࡢࣄࢺ࡟࠾ࡅࡿ⏕╔㒊఩࡛ࡢ⭘⒆ᙧᡂ⬟ࢆホ౯ࡍࡿࡓࡵࡢヨ㦂ࠊࡢ
3 ✀㢮ࡀ࠶ࡿࠋձࠊղࠊճࡢヨ㦂࡟ࡘ࠸࡚ࡣࠊࡑࢀࡒࢀ ࠊࠊ 㡯࡛㏙࡭ࡿࠋ≉࡟ࡇࢀࡽࡢ࠺ࡕղࡢ౛࡜ࡋ࡚ࠊ࠸ࡃࡘ࠿ࡢ in vitro ヨ㦂ἲཪࡣ in vivo ヨ㦂ἲࢆ⾲㸯ཬࡧ⾲㸰࡟౛♧ࡋࡓࠋ㐀⭘⒆ᛶࡢホ౯࡟࠾࠸࡚ࡣࠊྛヨ㦂ἲࡢཎ⌮ࢆ⌮ゎࡋࠊ᳨ฟ㝈⏺➼ࡢᛶ⬟ࢆ☜ㄆࡋࡓୖ࡛ࠊヨ㦂ἲࢆྲྀᤞ㑅ᢥࡋࠊ┠ⓗ࡟ᛂࡌࡓホ౯⣔ࢆࢹࢨ࢖ࣥࡍࡿࡇ࡜ࠋ
ཎᩱ࣭ཎᮦᩱࡢရ㉁≉ᛶホ౯࣭ရ㉁⟶⌮ࡢࡓࡵࡢ㐀⭘⒆ᛶヨ㦂ࣄࢺ ES/iPS ⣽⬊ຍᕤ〇ရࢆ〇㐀ࡍࡿࡓࡵࡢ⣽⬊ᇶᮦ࡜ࡋ࡚ࠊࣄࢺ ES ⣽⬊ཪࡣࣄࢺ iPS ⣽⬊ࡢࢭ࣭ࣝࣂࣥࢡࢆᶞ❧ࡋࡓ㝿࡟ࠊࢭ࣭ࣝࣂࣥࢡ୰ࡢ⣽⬊ࡢቑṪᛶ࡜ከ⬟ᛶࢆ᳨ドࡍࡿࡓࡵ࡟ࢸࣛࢺ࣮࣐ᙧᡂ⬟࡟ࡼࡿ㐀⭘⒆ᛶࢆ☜ㄆࡍࡿࡇ࡜ࡀ࠶ࡿࠋࡇࡢ㝿ࡢ㐀⭘⒆ᛶヨ㦂࡟ᙜࡓࡗ࡚ࡣࠊୡ⏺ಖ೺ᶵ㛵㸦WHO㸧ࡢ⏕≀⸆ရᶆ‽໬ᑓ㛛ጤဨ఍➨ 61 ḟሗ࿌㸦Technical Report
Series No. 978㸦WHO TRS 978㸧ᖹᡂ 25 ᖺ㸧ࡢ Annex 31 ࡀཧ⪃࡟࡞ࡿࠋ୰㛫〇ရཪࡣ᭱⤊〇ရࡢ㐀⭘⒆ᛶ⣽⬊ࡢΰᅾࢆホ౯ࡍࡿࡓࡵࡢヨ㦂ࣄࢺ ES/iPS ⣽⬊ຍᕤ〇ရࡢ୰㛫〇ရཪࡣ᭱⤊〇ရ࡜࡞ࡿ⣽⬊㞟ᅋ࡟ࡣࠊ┠ⓗ⣽⬊ཪࡣࡑࡢ๓㥑⣽⬊࡟ຍ࠼ࠊᮍศ໬࡞ࣄࢺ ES/iPS ⣽⬊ཬࡧࡑࡢ௚ࡢ┠ⓗእ⣽⬊ࡀΰᅾࡋ࡚࠸ࡿྍ⬟ᛶࡀ࠶ࡿࠋࣄࢺ ES/iPS ⣽⬊ࡣࢸࣛࢺ࣮࣐ᙧᡂ⬟࡟ࡼࡿ㐀⭘⒆ᛶࢆඖ᮶ࡢ≉ᛶ࡜ࡋ࡚ಖᣢࡋ
࡚࠸ࡿࡇ࡜࠿ࡽࠊ୰㛫〇ရཪࡣ᭱⤊〇ရ࡟࠾ࡅࡿᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࡢΰᅾ㔞ࢆࠊ⭘⒆
ࢆᙧᡂࡍࡿ࠾ࡑࢀࡢ࠶ࡿ┠ⓗእ⣽⬊࡛࠶ࡿᙧ㉁㌿᥮⣽⬊ࡢΰᅾ㔞࡜࡜ࡶ࡟ရ㉁≉ᛶ㸦㐀⭘⒆ᛶ⣽⬊ࡢΰᅾ㸧࡜ࡋ࡚ホ౯ࡋࠊ⟶⌮ࡍࡿࡇ࡜ࡀᚲせ࡛࠶ࡿࠋ୰㛫〇ရ࣭᭱⤊〇ရࡢᮍศ໬ከ⬟ᛶᖿ⣽⬊᳨ฟヨ㦂LQYLWUR ヨ㦂୰㛫〇ရཪࡣ᭱⤊〇ရࡢ୰࡟ΰᅾࡍࡿᮍศ໬ࣄࢺ ES/iPS ⣽⬊࡟㛵ࡋ࡚ࡣࠊࣄࢺ ES/iPS ⣽⬊ࡢศᏊ࣐࣮࣮࢝ࢆ᳨ฟࡍࡿࡇ࡜࡟ࡼࡗ࡚ホ౯ࡍࡿࡇ࡜ࡀྍ⬟࡛࠶ࡿࠋ᪉ἲ࡜ࡋ࡚ࡣࣇࣟ
࣮ࢧ࢖ࢺ࣓ࢺ࣮ࣜࡸᐃ㔞 RT-PCR 2,3ࠊཬࡧᇵ㣴ୖΎ୰ࡢ H3+࣏ࢻ࢝ࣜ࢟ࢩࣥࢆ᳨ฟࡍࡿ᪉ἲ
4ࠊ࣑ࣛࢽࣥ 521 ࡟ࡼࡿࣄࢺከ⬟ᛶᖿ⣽⬊┤᥋ᇵ㣴ቑᖜἲ 5 ࡞࡝ࡀᣲࡆࡽࢀࡿࠋࡓࡔࡋࠊ౑

⏝ࡍࡿศᏊ࣐࣮࣮࢝ࡢጇᙜᛶࡣࠊヨ㦂ᑐ㇟࡜࡞ࡿ⣽⬊✀ࡈ࡜࡟ணࡵ☜ㄆࡋ࡚࠾ࡃᚲせࡀ࠶ࡿࠋ౛࠼ࡤ LIN28 ࡣᵝࠎ࡞ṇᖖࣄࢺศ໬⣽⬊࣭ࣄࢺ⤌⧊࡟࠾࠸࡚Ⓨ⌧ࡀㄆࡵࡽࢀࡎࠊඃࢀࡓ
ࣄࢺ ES/iPS ⣽⬊ࡢ࣐࣮࣮࢝࡜⪃࠼ࡽࢀ࡚࠸ࡿࡀ 2,3ࠊࣄࢺ iPS ⣽⬊࠿ࡽ㛫ⴥ⣔ᖿ⣽⬊࡬ࡢศ㸫㸫

໬ㄏᑟ࡟࠾࠸࡚ࡣࠊiPS ⣽⬊࣐࣮࣮࢝࡜ࡋ࡚ࡢ≉␗ᛶࡣ㧗ࡃ࡞࠸ࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ 5ࠋ࡞࠾ࠊࣄࢺ ES/iPS ⣽⬊ࡣ㓝⣲ฎ⌮➼࡟ࡼࡾ༢⣽⬊࡟ࡲ࡛ศᩓࡍࡿ࡜࢔࣏ࢺ࣮ࢩࢫࢆ㉳ࡇࡍᛶ㉁ࢆࡶࡘࡓࡵࠊ㌾ᐮኳࢥࣟࢽ࣮ᙧᡂヨ㦂࡟ࡼࡾΰᅾࡍࡿᮍศ໬࡞ࣄࢺ ES/iPS ⣽⬊ࢆ᳨ฟࡍࡿࡇ࡜ࡣ࡛ࡁ࡞࠸ 2ࠋLQYLYR ヨ㦂〇ရ୰ࡢᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࡢΰᅾࡣࠊ㐺ษ࡞⣽⬊≉ᛶᣦᶆࢆ⏝࠸࡚ in vitro ヨ㦂᳨࡛ᰝࡋࠊホ౯ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋࡓࡔࡋࠊ〇ရ࡟࠾ࡅࡿᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࡢΰᅾ㔞ࡣࠊච␿୙඲ື≀࡛ࡢ㐀⭘⒆ᛶࢆᣦᶆ࡟ࡋ࡚ホ౯ࡍࡿࡇ࡜ࡶᚲ㡲࡛ࡣ࡞࠸ࡀྍ⬟࡛࠶ࡿࠋච␿
୙඲ື≀࡜ࡋ࡚ࡣࠊNOD.Cg-Prkdcscid Il2rgtm1Sug/Jic ࣐࢘ࢫ㸦௨ୗࠕNOG ࣐࢘ࢫࠖ࡜࠸࠺ࠋ
㸧6ࠊ
NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ ࣐࢘ࢫ㸦௨ୗࠕNSG ࣐࢘ࢫࠖ࡜࠸࠺ࠋ
㸧 7 ࡞࡝ࡢ㔜ᗘච␿୙඲
࣐࢘ࢫ⣔⤫ࡀᣲࡆࡽࢀࡿࠋࡇࢀࡽࡢ࣐࢘ࢫࡣ T ⣽⬊ࠊB ⣽⬊ཬࡧ NK ⣽⬊ࢆḞኻࡋ࡚࠾ࡾࠊ
ࢾ࣮ࢻ࣐࢘ࢫ࡜ẚ࡭࡚ࣄࢺࡢ⣽⬊ࡸ⤌⧊ࡢ⏕╔ᛶࡀ㧗࠸ 8,9,10ࠋC.Cg-Rag2tm1Fwa Il2rgtm1Sug/Jic࣐࢘ࢫ㸦௨ୗࠕBRG࣐ࠖ࢘ࢫ㸧࡜࠸࠺ࠋ㸧ࡶ T ⣽⬊ࠊB ⣽⬊ཬࡧ NK ⣽⬊ࢆḞኻࡋࡓ⣔⤫ࡔࡀࠊࣄࢺ㐀⾑ᖿ⣽⬊ࡢ⏕╔ᛶࡀ NOG ࣐࢘ࢫࡸ NSG ࣐࢘ࢫࡼࡾࡶప࠸ࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ
11,12ࠋSCID ࣐࢘ࢫࡸ NOD/SCID ࣐࢘ࢫ࡟ࡘ࠸࡚ࡣࠊ⮬↛Ⓨ⏕ⓗ࡞⬚⭢⭘ࡀぢࡽࢀࡿࡓࡵࠊ㛗ᮇほᐹࡀᚲせ࡜࡞ࡿ㐀⭘⒆ᛶヨ㦂┠ⓗ࡛ࡣࠊ౑⏝ࢆ᥎ዡࡋ࡞࠸ࠋWHO TRS 978 ࡛᥎ዡࡉࢀࡿࢾ࣮ࢻ࣐࢘ࢫࢆ⏝࠸ࡿ᪉ἲࡣࠊഹ࠿࡟ṧᏑࡍࡿᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࢆ᳨ฟࡍࡿ࡟ࡣ
ឤᗘࡀపࡃࠊ⤖ᯝࡀഇ㝜ᛶ࡟࡞ࡗ࡚ࡋࡲ࠺ᜍࢀࡀ࠶ࡿࡓࡵࠊ〇ရࡢᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࡢΰᅾࢆホ౯ࡍࡿ┠ⓗ࡟ࡣ㐺ࡉ࡞࠸ 10ࠋᢞ୚㒊఩࡟ࡘ࠸࡚ࡣࠊᡭᢏࡀ⡆༢࡛ࠊᡭᢏ⇍⦎ᗘ࡟ࡼࡿ⤖ᯝࡢࣂࣛࢶ࢟ࢆ㜵ࡆࡿࡇ࡜ࠊከࡃࡢ〇ရ⣽⬊ࢆᢞ୚ࡍࡿࡇ࡜ࡀྍ⬟࡛࠶ࡿࡇ࡜ࠊ࠿ࡘࠊᐜ᫆࡟⭘⒆ᙧᡂࡢ᫬㛫⤒㐣ࢆほᐹࡍࡿࡇ࡜ࡀ࡛ࡁࡿࡇ࡜࠿ࡽࠊ⫼㒊⓶ୗࡀ୍⯡ⓗ࡟⏝࠸ࡽࢀࡿࠋᢞ୚㒊఩ࡢほᐹ᪉ἲ࡟㛵ࡋ࡚ࡣࠊ5.3.6.㡯ࢆཧ⪃࡟ࡍࡿࡇ࡜ࠋ
〇ရ⣽⬊࡟ΰᅾࡍࡿᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࢆᐃ㔞໬ࡍࡿࡢࡳࡢ┠ⓗ࡛ in vivo ヨ㦂ࢆᐇ᪋ࡍࡿࡇ࡜ࡣ౛እⓗ࡜⪃࠼ࡽࢀࡿࡀࠊ௬࡟ࡑ࠺ࡋࡓ┠ⓗࡢࡓࡵ࡟ヨ㦂ࡍࡿ࡟ࡣࠊ㝧ᛶᑐ↷⣽⬊ࡢྠ➼࡞᮲௳㸦ᢞ୚㒊఩࣭᪉ἲ㸧࡛ࡢ⣽⬊⛣᳜࡟ࡼࡿヨ㦂ࡢタᐃࡀࠊ〇ရ⣽⬊ࡢヨ㦂᫬ཪࡣ஦๓᳨ウ࡟࠾࠸࡚ᚲ㡲࡛࠶ࡿࠋ㝧ᛶᑐ↷⣽⬊࡜ࡋ࡚ࡣࠊ〇ရ୰ࡢᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࡢṧᏑࢆᑐ㇟࡜ࡍࡿࡢ࡛࠶ࢀࡤࠊ୍⯡࡟ࠊ〇ရ⣽⬊࡟ΰᅾࡍࡿྍ⬟ᛶࡀ⪃࠼ࡽࢀࡿ〇ရࡢ〇㐀⏝⣽⬊ᇶᮦ࡛࠶ࡿᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࢆ⏝࠸ࡿࠋ〇ရ⣽⬊ࢆᢞ୚ࡍࡿ㝿࡟ࡣࠊ⣽⬊ࢆ࣐ࢺࣜࢤࣝ࡟ᠱ⃮ࡋ࡚ᢞ୚ࡋࡓ᪉ࡀ᳨ฟឤᗘࡣ㧗ࡃ࡞ࡿ 8,10,13,14ࠋ࡞࠾ࠊࣄࢺ ES/iPS ⣽⬊ࡣࢺࣜࣉࢩࣥฎ⌮➼࡟ࡼࡿ༢୍⣽⬊࡬ࡢศᩓ࡟ࡼࡾ࢔࣏ࢺ࣮ࢩࢫࢆ㉳ࡇࡍᛶ㉁ࢆᣢࡘࡓࡵࠊ࣐
࢘ࢫ࡬ࡢᢞ୚᫬࡟ࡣࡇࢀࢆ㜵ࡄᑐ⟇ࡀᚲせ࡛࠶ࡿࠋศᩓㄏᑟᛶ࢔࣏ࢺ࣮ࢩࢫ㜵Ṇ⟇࡜ࡋ࡚ࡣࠊࢺࣜࣉࢩࣥฎ⌮➼ࢆ⾜ࢃࡎ࡟〇ရࢆᢞ୚ࡍࡿ᪉ἲ௨እ࡟ࠊࢺࣜࣉࢩࣥฎ⌮➼࡟ࡼࡾศᩓ
ࡋࡓ〇ရ⣽⬊ࢆ ROCK 㜼ᐖ⸆ཬࡧࣄࢺ᪂⏕ඣ⏤᮶⥺⥔ⱆ⣽⬊࡜࡜ࡶ࡟࣐ࢺࣜࢤࣝ࡟ᠱ⃮ࡋ࡚ᢞ୚ࡍࡿ 15,16 ࡞࡝ࡢ᪉ἲࡀ࠶ࡿࠋ〇ရ⣽⬊ࡢ⛣᳜࡛ࡣࠊᐇ㝿ࡢ⮫ᗋᛂ⏝᫬ࡢ⣽⬊⏝㔞ࢆ຺᱌ࡋࠊ⛣᳜⾜Ⅽ⮬యࡶ࢔࣮ࢳࣇ࢓ࢡࢺࡀ⏕ࡌ࡞࠸⠊ᅖ࡛ࠊ࡛ࡁࡿࡔࡅከࡃࡢ〇ရ⣽⬊ࢆ⛣᳜㸫㸫

ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋࡲࡓヨ㦂ື≀ࡢᩘࡣࠊ⛣᳜⾜Ⅽࡢ㞴᫆ᗘࡸヨ㦂ື≀ࡢ⏕Ꮡ⋡➼ࢆ⪃៖ࡋࡓୖ࡛タᐃࡍࡿࠋ ⩌࡟ࡘࡁ᭱⤊ホ౯ྍ⬟࡞༉ᩘ࡜ࡋ࡚ 10 ༉௨ୖ࡛ᐇ᪋ࡍࡿࡇ࡜ࡀᮃࡲ
ࡋ࠸ࡀࠊ㸯⩌࡟ࡘࡁ᭱⤊ホ౯ྍ⬟࡞༉ᩘ࡜ࡋ࡚᭱ప࡛ࡶ 6 ༉௨ୖ࡛ᐇ᪋ࡍࢀࡤࠊᐃ㔞ⓗ ᐃ㡯┠࡟࠾ࡅࡿࢹ࣮ࢱࡢࣂࣛࢶ࢟ࡀẕ㞟ᅋࡢࣂࣛࢶ࢟ࢆᴫࡡ཯ᫎࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀࡿࠋ
㝧ᛶᑐ↷⣽⬊࡜ྠᵝ࡞ᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࡢṧᏑࢆ᝿ᐃࡋࡓୖ࡛ヨ㦂ࢆ⾜࠺ࡢ࡛ࠊ〇ရ⣽⬊ࡢᢞ୚᫬࡟౑⏝ࡍࡿᇵᆅࡣࠊࣄࢺ࡟ᢞ୚ࡍࡿ㝿࡟⏝࠸ࡽࢀࡿࡶࡢࡼࡾࡶ㝧ᛶᑐ↷⣽⬊ࡢቑṪ࡟㐺ࡋࡓࡶࡢࡀ฼⏝ྍ⬟࡞ࡽࡤࠊࡑࢀࢆ౑⏝ࡍࡿࠋ୰㛫〇ရཪࡣ᭱⤊〇ရ࡟࠾ࡅࡿᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࡢΰᅾ㔞ࢆホ౯ࡍࡿࡓࡵ࡟ࠊ〇ရ⣽⬊ཪࡣ㝜ᛶᑐ↷⣽⬊࡜࡞ࡿࣄࢺ஧ಸయ⣽⬊࡟ᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࢆࢫࣃ࢖ࢡࡋࡓ㝧ᛶᑐ↷⩌ࢆタᐃࡍࡿࡇ࡜ࡀᚲせ࡛࠶ࡿࠋ㝜ᛶᑐ↷⩌࡟ࡘ࠸࡚ࡣࠊ㝜ᛶᑐ↷⣽⬊࡜࡞ࡿࣄࢺ஧ಸ
య⣽⬊ࡢධᡭ࡜฼⏝ࡢྍ⬟ᛶࢆ຺᱌ࡋ࡚ࠊࡑࡢタᐃࡢྍྰࢆ᳨ウࡍࡿࠋヨ㦂᫬ཪࡣ஦๓࡟᳨
ウࡍࡿ㝧ᛶᑐ↷⩌࡟࠾࠸࡚ࡣࠊ␗࡞ࡿ⏝㔞ࡢᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࢆྵࡴ⣽⬊ヨᩱࢆ⛣᳜ࡋࡓ」ᩘࡢ⩌ࢆタᐃࡋࠊ᭱ప⭘⒆ᙧᡂ⏝㔞㸦TPDmin㸸minimum tumor-producing dose㸧࡜⭘⒆
ฟ⌧ࡲ࡛ࡢᮇ㛫ࢆ☜ㄆࡍࡿᚲせࡀ࠶ࡿࠋほᐹᮇ㛫࡟ࡘ࠸࡚ࡣࠊ㝧ᛶᑐ↷⩌ࡢ୰ࡢ TPDmin ࡟࠾ࡅࡿ⭘⒆ᙧᡂ☜⋡ࡀ୍ᐃ್࡟㐩ࡍࡿ᫬Ⅼࢆ༑ศ㉸࠼ࡿᮇ㛫࡜ࡍࡿࠋ࡞࠾ࠊᮍศ໬ࣄࢺ ES/iPS ⣽⬊ࡢΰᅾࢆホ౯ࡍࡿࡇ࡜ࡀ┠ⓗࡢሙྜ࡟ࡣࠊヨ㦂⣔ࡢ⢭ᗘྥୖࡢࡓࡵ࡟∦ᛶࡢື≀ࡢࡳࢆ౑⏝ࡍࡿࡇ࡜ࡶチᐜࡉࢀ࠺ࡿࠋ
TPDmin ࡟࠾ࡅࡿ⭘⒆ᙧᡂ☜⋡ࢆࡶ࡜࡟ࠊ⿕㦂〇ရ࠿ࡽᚓࡽࢀࡓ⤖ᯝࡀഇ㝜ᛶ࡛࠶ࡿ☜⋡ࢆồࡵ࡚࠾ࡃࡇ࡜ࠋ࡞࠾ࠊTPDmin ௨ୖࡢΰᅾࡀ࡞࠸ࡇ࡜ࢆ⤫ィᏛⓗ☜࠿ࡽࡋࡉ࡜࡜ࡶ࡟♧ࡍࡓࡵࡢ༉ᩘࡢタᐃ᪉ἲࡶ▱ࡽࢀ࡚࠸ࡿ 8ࠋࡑࡢ௚ࡢᢏ⾡ⓗ࡞ヲ⣽࡟ࡘ࠸࡚ࡣࠊ5.3.6.㡯ࢆཧ⪃࡟ࡍࡿࡇ࡜ࠋ
࡞࠾୍⯡࡟ࡣࠊᮍศ໬ ES/iPS ⣽⬊᳨ฟ in vivo ヨ㦂ࡣࠊ୰㛫〇ရ࣭᭱⤊〇ရࡢᙧ㉁㌿᥮⣽⬊᳨ฟヨ㦂㸦5.2.2.2.㡯㸧ࢆවࡡ࡚ᐇ᪋ࡍࡿࡢࡀ⌧ᐇⓗ࡛࠶ࡿࠋ୰㛫〇ရ࣭᭱⤊〇ရࡢᙧ㉁㌿᥮⣽⬊᳨ฟヨ㦂LQYLWUR ヨ㦂୰㛫〇ရཪࡣ᭱⤊〇ရࡢ୰࡟ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊࡟㛵ࡋ࡚ࡣࠊ᪤ᐃࡢᇵ㣴ᮇ㛫ࢆ㉸࠼ࡓ⣽⬊ࡢቑṪ≉ᛶゎᯒ࡟ࡼࡿ୙Ṛ໬ࡋࡓᙧ㉁㌿᥮⣽⬊᳨ฟ 17,18 ࡸࠊ㌾ᐮኳࢥࣟࢽ࣮ᙧᡂヨ㦂 2,8 ཪࡣࢹࢪࢱࣝ㌾ᐮኳࢥࣟࢽ࣮ᙧᡂヨ㦂 19 ࡟ࡼࡿ㊊ሙ㠀౫ᏑᛶቑṪ⣽⬊㸦ᝏᛶᙧ㉁㌿᥮⣽⬊㸧ࡢ᳨ฟ࡞࡝࡟ࡼࡗ࡚ホ౯ࡀྍ⬟࡛࠶ࡿࠋࡓࡔࡋࠊ⮫ᗋ࡛ࡢ〇ရ౑⏝᫬࡟ࡣࠊ࠸ࡎࢀࡢ
in vitro ヨ㦂࡛ࡶ᳨ฟᅔ㞴࡞ᙧ㉁㌿᥮⣽⬊ࡢᏑᅾࡢྍ⬟ᛶࢆ⪃៖ࡋࡓ࠺࠼࡛ࣜࢫࢡホ౯ࢆ⾜࠺ࡇ࡜ࠋ⣽⬊ቑṪ≉ᛶゎᯒࡣࠊᙧ㉁㌿᥮࡟ࡼࡾ୙Ṛ໬ࡋࡓ⣽⬊ࢆࠊᝏᛶᗘࡢ᭷↓࡟࠿࠿ࢃࡽࡎ᳨ฟ
ࡍࡿࡇ࡜ࡢ࡛ࡁࡿヨ㦂࡛࠶ࡿࠋ୍᪉ࠊࢹࢪࢱࣝ㌾ᐮኳࢥࣟࢽ࣮ᙧᡂヨ㦂ࡣࠊ㧗࠸ឤᗘ࡛ᙧ㉁㌿᥮⣽⬊ࢆ᳨ฟࡍࡿࡇ࡜ࡀ࡛ࡁࡿヨ㦂࡛࠶ࡿࡀࠊ᳨ฟ࡛ࡁࡿࡢࡣ㊊ሙ㠀౫ᏑᛶቑṪ⬟ࢆᣢࡘ⣽⬊ࠊࡍ࡞ࢃࡕᝏᛶᗘࡢ㧗࠸ᙧ㉁㌿᥮⣽⬊࡟㝈ࡽࢀࡿࠋ㸫㸫

࠸ࡎࢀ࡟ࡋ࡚ࡶࠊ୰㛫〇ရཪࡣ᭱⤊〇ရ࡟࠾ࡅࡿᙧ㉁㌿᥮⣽⬊ࡢΰᅾ㔞ࢆホ౯ࡍࡿࡓࡵ
࡟ࠊ㝧ᛶᑐ↷⣽⬊࡜ࡍࡿ㐀⭘⒆ᛶᙧ㉁㌿᥮⣽⬊ࢆタᐃࡍࡿࠋࡲࡓヨ㦂ࢆ⾜࠺㝿࡟ࡣࠊ〇ရ⣽⬊ཪࡣ㝜ᛶᑐ↷⣽⬊࡜࡞ࡿࣄࢺ஧ಸయ⣽⬊࡟㝧ᛶᑐ↷⣽⬊ࢆࢫࣃ࢖ࢡࡋࡓ㝧ᛶᑐ↷⩌ࢆタࡅࡿࠋ⿕㦂〇ရ୰ࡢᙧ㉁㌿᥮⣽⬊ࡢΰᅾ㔞ࡣࠊΰᅾࡋ࠺ࡿᙧ㉁㌿᥮⣽⬊ࡢ㐀⭘⒆ᛶࢆ㝧ᛶᑐ↷⣽⬊࡜ྠ➼࡜௬ᐃࡋࡓ࠺࠼࡛ᐃ㔞໬ࡍࡿࡇ࡜ࡀ࡛ࡁࡿࠋΰᅾࡍࡿྍ⬟ᛶࡢ࠶ࡿᙧ㉁㌿᥮⣽⬊ࡢ≉ᛶࡀ࠶ࡽ࠿ࡌࡵ᥎ᐃࡉࢀ࡚࠾ࡾࠊ࠿ࡘࠊࡇࢀ࡟㢮ఝࡍࡿ⾲⌧ᆺࢆ♧ࡍ⣽⬊ᰴࡀ฼⏝ྍ⬟࡞ሙྜ௨እࡣࠊ⭘⒆ᙧᡂ⬟ࡀⰋࡃ◊✲ࡉࢀㄆ▱ࡉࢀ࡚࠸ࡿ HeLa ⣽⬊➼ࢆ㝧ᛶᑐ↷⣽⬊࡜ࡋ࡚౑⏝ࡍࡿࠋ࡞࠾ࠊ㝧ᛶᑐ↷⣽⬊࡟ࡣࠊ㐺ษ࡟ရ㉁⟶⌮ࡉࢀࡓ⣽⬊ᥦ౪ᶵ㛵࠿ࡽධᡭࡋ
ࡓ⣽⬊ᰴࢆ౑⏝ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ
ࡇࢀࡽࡢ᪤Ꮡࡢ in vitro ヨ㦂࡛タᐃࡉࢀࡓᇵ㣴᮲௳࡛〇ရ⣽⬊ࡀᇵ㣴࡛ࡁ࡞࠸ሙྜ࡛࠶ࡗ
࡚ࠊ୰㛫〇ရཪࡣ᭱⤊〇ရࡢ୰࡟ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊࡟≉ᚩⓗ࡞㑇ఏᏊࡸศᏊࢆྠᐃࡍ
ࡿࡇ࡜ࡀྍ⬟࡞ሙྜࡣࠊ✀ࠎࡢࣂࣜࢹ࣮ࢩࣙࣥヨ㦂ࢆᐇ᪋ࡋࡓୖ࡛ᇵ㣴ࢆࡏࡎ࡟ࠊศᏊ⏕≀Ꮫⓗ࡟ΰᅾࡀᐃ㔞໬࡛ࡁࡿࡼ࠺࡞᳨ฟ⣔ࡢタᐃࢆ⾜࠺ࡇ࡜ࡀ⪃࠼ࡽࢀࡿࡀࠊᴟࡵ࡚ಶูⓗ࡞ヨ㦂࡜࡞ࡿࡢ࡛ࠊ୍⯡ⓗᢏ⾡せồ࡜ࡍࡿࡇ࡜ࡸᶆ‽ἲࢆᮏᩥ᭩࡛♧ࡍࡇ࡜ࡣ࡛ࡁ࡞࠸ࠋ
LQYLYR ヨ㦂〇ရ୰ࡢ⭘⒆ᙧᡂ⬟ࢆᣢࡘᙧ㉁㌿᥮⣽⬊ࡢΰᅾࡣࠊ㐺ษ࡞⣽⬊≉ᛶᣦᶆࢆ⏝࠸࡚ in vitro
ヨ㦂᳨࡛ᰝࡋࠊホ౯ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋࡓࡔࡋࠊ〇ရ࡟࠾ࡅࡿᙧ㉁㌿᥮⣽⬊ࡢΰᅾ㔞ࡣච␿୙඲ື≀࡛ࡢ㐀⭘⒆ᛶࢆᣦᶆ࡟ࡋ࡚ホ౯ࡍࡿࡇ࡜ࡶᚲ㡲࡛ࡣ࡞࠸ࡀྍ⬟࡛࠶ࡿࠋච␿୙
඲ື≀࡜ࡋ࡚ࡣࠊNOG ࣐࢘ࢫ 6ࠊNSG ࣐࢘ࢫ 7 ࡞࡝ࡢ㔜ᗘච␿୙඲࣐࢘ࢫ⣔⤫ࡀᣲࡆࡽࢀ
ࡿࠋࡇࢀࡽࡢ࣐࢘ࢫࡣ T ⣽⬊ࠊB ⣽⬊ཬࡧ NK ⣽⬊ࢆḞኻࡋ࡚࠾ࡾࠊࢾ࣮ࢻ࣐࢘ࢫ࡜ẚ࡭࡚ࣄࢺࡢ⣽⬊ࡸ⤌⧊ࡢ⏕╔ᛶࡀ㧗࠸ 8,9,10ࠋࢺࣜࣉࢩࣥฎ⌮࡞࡝࡟ࡼࡾศᩓࡋࡓ〇ရ⣽⬊ࢆᢞ୚ࡍࡿሙྜ࡟ࡣࠊ⣽⬊ࢆ࣐ࢺࣜࢤࣝ࡟ᠱ⃮ࡋ࡚ᢞ୚ࡋࡓ᪉ࡀ᳨ฟឤᗘࡣ㧗ࡃ࡞ࡿ 8,10,13,14ࠋBRG
࣐࢘ࢫࡶ T ⣽⬊ࠊB ⣽⬊ཬࡧ NK ⣽⬊ࢆḞኻࡋࡓ⣔⤫ࡔࡀࠊࣄࢺ㐀⾑ᖿ⣽⬊ࡢ⏕╔ᛶࡀ NOG
࣐࢘ࢫࡸ NSG ࣐࢘ࢫࡼࡾࡶప࠸ࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ 11,12ࠋSCID ࣐࢘ࢫࡸ NOD/SCID ࣐࢘ࢫ࡟ࡘ࠸࡚ࡣࠊ⮬↛Ⓨ⏕ⓗ࡞⬚⭢⭘ࡀぢࡽࢀࡿࡓࡵࠊ㛗ᮇほᐹࡀᚲせ࡜࡞ࡿ㐀⭘⒆ᛶヨ㦂┠ⓗ࡛ࡣ౑⏝ࢆ᥎ዡࡋ࡞࠸ࠋWHO TRS 978 ࡛᥎ዡࡉࢀࡿࢾ࣮ࢻ࣐࢘ࢫࢆ⏝࠸ࡿ᪉ἲࡶࠊഹ࠿
࡟ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊ࢆ᳨ฟࡍࡿ࡟ࡣឤᗘࡀపࡃࠊ⤖ᯝࡀഇ㝜ᛶ࡟࡞ࡗ࡚ࡋࡲ࠺ᜍࢀࡀ
࠶ࡿࡓࡵࠊᮏ㡯ࡢ┠ⓗ࡟ࡣ㐺ࡉ࡞࠸ 8ࠊ10ࠋ୰㛫〇ရཪࡣ᭱⤊〇ရ࡟࠾ࡅࡿᙧ㉁㌿᥮⣽⬊ࡢΰᅾ㔞ࢆホ౯ࡍࡿ㝿࡟ࡣࠊ㝧ᛶᑐ↷⣽⬊࡜ࡍࡿᙧ㉁㌿᥮⣽⬊ࢆタᐃࡍࡿᚲせࡀ࠶ࡿࠋࡍ࡞ࢃࡕࠊ㝧ᛶᑐ↷⣽⬊ࢆ〇ရ⣽⬊ཪࡣ㝜ᛶᑐ↷⣽⬊࡜࡞ࡿࣄࢺ஧ಸయ⣽⬊࡟ࢫࣃ࢖ࢡࡋࡓ㝧ᛶᑐ↷⩌ࢆタᐃࡋࠊ〇ရ⣽⬊ࡢヨ㦂᫬ཪࡣ஦๓᳨ウ࡟࠾࠸࡚ࠊࡑࡢ㐀⭘⒆ᛶࢆ☜ㄆࡍࡿࠋタᐃࡋࡓ㝧ᛶᑐ↷⩌࡟࠾࠸࡚ࡣࠊ␗࡞ࡿ⏝㔞ࡢ㝧ᛶᑐ↷⣽⬊ࢆྵࡴ⣽⬊ヨᩱࢆ⛣᳜ࡋࡓ」ᩘࡢ⩌ࢆタᐃࡋࠊTPDmin ࡜⭘⒆ฟ⌧ࡲ࡛ࡢᮇ㛫ࢆ࠶ࡽ࠿ࡌࡵ☜ㄆࡋ࡚࠾ࡃࠋࡇࡢࡼ࠺࡞᳨ウࢆ⾜࠺ࡇ࡜࡟ࡼࡾࠊ〇ရ⣽⬊୰ࡢᙧ㉁㌿᥮⣽⬊ࡢᐃ㔞ⓗホ౯ࡀྍ⬟࡜࡞ࡿࠋ㸫㸫

ΰᅾࡍࡿྍ⬟ᛶࡢ࠶ࡿᙧ㉁㌿᥮⣽⬊ࡢ≉ᛶࡀ࠶ࡽ࠿ࡌࡵ᥎ᐃࡉࢀ࡚࠾ࡾࠊ࠿ࡘࡇࢀ࡟㢮ఝࡍࡿ⾲⌧ᆺࢆ♧ࡍ⣽⬊ᰴࡀ฼⏝ྍ⬟࡛࠶ࡿሙྜ௨እࡣࠊ⭘⒆ᙧᡂ⬟ࡀⰋࡃ◊✲ࡉࢀㄆ▱ࡉࢀ࡚࠸ࡿ HeLa ⣽⬊➼ࢆ㝧ᛶᑐ↷⣽⬊࡜ࡋ࡚౑⏝ࡍࡿࠋ⏝㔞ࡢ␗࡞ࡿ㝧ᛶᑐ↷⣽⬊ࢆࢫࣃ࢖ࢡࡋࡓ㝧ᛶᑐ↷⩌ࢆタᐃࡋࠊ㝧ᛶᑐ↷⣽⬊ࡢ TPDmin ࢆ஦๓࡟ホ౯ࡋ࡚࠾ࡃࠋ⟬ฟࡉࢀࡿ
ᙧ㉁㌿᥮⣽⬊ࡢΰᅾ㔞ࡣࠊ࠶ࡃࡲ࡛ΰᅾࡋ࠺ࡿᙧ㉁㌿᥮⣽⬊ࡢ㐀⭘⒆ᛶࢆ㝧ᛶᑐ↷⣽⬊࡜ྠ➼࡜௬ᐃࡋࡓ࠺࠼࡛ᐃ㔞໬ࡉࢀࡓࡶࡢ࡛࠶ࡿࡇ࡜࡟ὀពࡍࡿࡇ࡜ࠋ࡞࠾ࠊ㝧ᛶᑐ↷⣽⬊࡟ࡣࠊ㐺ษ࡟ရ㉁⟶⌮ࡉࢀࡓ⣽⬊ᥦ౪ᶵ㛵࠿ࡽධᡭࡋࡓ⣽⬊ᰴࢆ౑⏝ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ
ᢞ୚㒊఩࡟ࡘ࠸࡚ࡣࠊᡭᢏࡀ⡆༢࡛ࠊᡭᢏ⇍⦎ᗘ࡟ࡼࡿ⤖ᯝࡢࣂࣛࢶ࢟ࢆ㜵ࡆࡿࡇ࡜ࠊከ
ࡃࡢ〇ရ⣽⬊ࢆᢞ୚ࡍࡿࡇ࡜ࡀྍ⬟࡛࠶ࡿࡇ࡜ࠊ࠿ࡘࠊᐜ᫆࡟⭘⒆ᙧᡂࡢ᫬㛫⤒㐣ࢆほᐹࡍࡿࡇ࡜ࡀ࡛ࡁࡿࡇ࡜࠿ࡽࠊ⫼㒊⓶ୗࡀ୍⯡ⓗ࡟⏝࠸ࡽࢀࡿࡀࠊ⮫ᗋୖࡢ⛣᳜⤒㊰ࡸ⛣᳜㒊఩࡜㐀⭘⒆ᛶ࡜ࡢ㛵㐃࡟ࡘ࠸࡚≉࡟㛵ᚰࡀ㧗࠸ሙྜ㸦5.3 㡯ཧ↷㸧࡟ࡣࠊྍ⬟࡞⠊ᅖ࡛⮫ᗋ㐺⏝࡜ྠᵝ࡜ࡍࡿࡇ࡜ࢆ⪃៖ࡍࡿࠋᢞ୚㒊఩ࡢほᐹ᪉ἲ࡟㛵ࡋ࡚ࡣࠊ5.3.6.㡯ࢆཧ⪃࡟ࡍࡿࡇ࡜ࠋヨ㦂᫬ཪࡣ஦๓᳨ウ࡟࠾࠸࡚ࠊ㝧ᛶᑐ↷⩌ࡢ୰࡛⭘⒆ᙧᡂࡀㄆࡵࡽࢀࡿ TPDmin ࢆ☜ㄆࡍࡿ࡜࡜ࡶ࡟ࠊ㝧ᛶᑐ↷⩌ࡢ୰ࡢ TPDmin ࡟࠾ࡅࡿ⭘⒆ᙧᡂ☜⋡ࡀ୍ᐃ್࡟㐩ࡍࡿ᫬Ⅼࢆ༑ศ㉸࠼ࡓ᫬Ⅼࡲ࡛ほᐹࡍࡿࠋࡑࡢ㝿ࠊ⛣᳜ࡋࡓື≀ࡢ 50%࡟⭘⒆ࡀฟ᮶ࡿ⏝㔞㸦TPD50㸸 tumorproducing dose at the 50% end-point㸧1 ࢆ⟬ฟࡋ࡚࠾ࡃࡇ࡜ࡶ᭷⏝࡛࠶ࡿࠋTPD50 ್ࡣ㝧ᛶᑐ↷⣽⬊ࡢ㐀⭘⒆ᛶࢆᐃ㔞ⓗ࡟♧ࡍᣦᶆ࡛࠶ࡾࠊ〇ရ⣽⬊୰ࡢᙧ㉁㌿᥮⣽⬊ࡢ㐀⭘⒆ᛶࢆ㆟ㄽ
ࡍࡿ㝿ࡢẚ㍑ᑐ㇟࡜࡞ࡿࠋヨ㦂ື≀ࡢᩘࡣࠊ⛣᳜⾜Ⅽࡢ㞴᫆ᗘࡸヨ㦂ື≀ࡢ⏕Ꮡ⋡➼ࢆ⪃៖ࡋࡓୖ࡛タᐃࡍࡿࠋ㸯⩌࡟ࡘࡁ᭱⤊ホ౯ྍ⬟࡞༉ᩘ࡜ࡋ࡚ 10 ༉௨ୖ࡛ᐇ᪋ࡍࡿࡇ࡜ࡀᮃࡲ
ࡋ࠸ࡀࠊ㸯⩌࡟ࡘࡁ᭱⤊ホ౯ྍ⬟࡞༉ᩘ࡜ࡋ࡚᭱ప࡛ࡶ㸴༉௨ୖ࡛ᐇ᪋ࡍࢀࡤࠊᐃ㔞ⓗ ᐃ㡯┠࡟࠾ࡅࡿࢹ࣮ࢱࡢࣂࣛࢶ࢟ࡀẕ㞟ᅋࡢࣂࣛࢶ࢟ࢆᴫࡡ཯ᫎࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀࡿࠋ
〇ရ⣽⬊࡜ྠ᫬࡟ᢞ୚ࡍࡿᇵᆅ࡜ࡋ࡚ࠊ〇ရ⣽⬊ࡢቑṪཪࡣ⏕Ꮡ࡟㐺ࡋࡓᇵᆅࢆ౑⏝ࡍࡿሙྜ࡟ࡣࠊࡑࡢᇵᆅ࡛ࡶ㝧ᛶᑐ↷⣽⬊ࡢ㐀⭘⒆ᛶࡀಖᣢࡉࢀ࡚࠸ࡿࡇ࡜ཪࡣቑṪࡀ㜼ᐖࡉࢀ࡞࠸ࡇ࡜ࡀ☜ㄆࡉࢀࡿᚲせࡀ࠶ࡿⅬ࡟ὀពࡍࡿࠋ㝧ᛶᑐ↷⣽⬊ࡢቑṪ࡟㐺ࡋࡓᇵᆅࢆ
౑⏝ࡍࡿሙྜࡣࠊ〇ရ⣽⬊୰࡟ΰᅾࡍࡿྍ⬟ᛶࡢ࠶ࡿᙧ㉁㌿᥮⣽⬊ࡢ୰࡟ࡣࠊࡑࡢᇵᆅࡀ⏕ᏑࡸቑṪ࡟㐺ࡉ࡞࠸ࡶࡢࡶ࠶ࡾ࠺ࡿࡇ࡜࡟ὀពࡍࡿᚲせࡀ࠶ࡿࠋ〇ရ⣽⬊ࡢ⛣᳜࡛ࡣࠊᐇ㝿ࡢ⮫ᗋᛂ⏝᫬ࡢ⣽⬊⏝㔞ࢆ຺᱌ࡋࠊ⛣᳜⾜Ⅽ⮬యࡶ࢔࣮ࢳࣇ࢓
ࢡࢺࡀ⏕ࡌ࡞࠸⠊ᅖ࡛ࠊ࡛ࡁࡿࡔࡅከࡃࡢ〇ရ⣽⬊ࢆ⛣᳜ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ⭘⒆ࡀほᐹࡉࢀ࡞࠿ࡗࡓሙྜࡣࠊ⿕㦂〇ရ࠿ࡽᚓࡽࢀࡓ⤖ᯝࡀഇ㝜ᛶ࡛࠶ࡿ☜⋡ࢆࠊ㝧ᛶᑐ↷⣽⬊ࡢ
TPDmin ࡟࠾ࡅࡿ⭘⒆ᙧᡂ☜⋡ࢆࡶ࡜࡟ࡋ࡚ồࡵ࡚࠾ࡃࡇ࡜ࠋ࡞࠾ࠊTPDmin ௨ୖࡢΰᅾࡀ࡞
࠸ࡇ࡜ࢆ⤫ィᏛⓗ☜࠿ࡽࡋࡉ࡜࡜ࡶ࡟♧ࡍࡓࡵࡢ༉ᩘࡢタᐃ᪉ἲࡶ▱ࡽࢀ࡚࠸ࡿ 8ࠋࡑࡢ௚ࡢᢏ⾡ⓗ࡞ヲ⣽࡟ࡘ࠸࡚ࡣࠊ5.3.㡯ࢆཧ⪃࡟ࡍࡿࡇ࡜ࠋ࡞࠾ࠊ㐀⭘⒆ᛶࢆᣢࡘᙧ㉁㌿᥮⣽⬊ࡢΰᅾࢆホ౯ࡍࡿࡇ࡜ࡀ┠ⓗࡢሙྜ࡟ࡣࠊヨ㦂⣔ࡢ⢭ᗘྥୖࡢࡓࡵ࡟∦ᛶࡢື≀ࡢࡳࢆ౑⏝ࡍࡿࡇ࡜ࡶチᐜࡉࢀ࠺ࡿࠋࡲࡓࠊ㝜ᛶᑐ↷⩌࡟ࡘ࠸࡚ࡣࠊ㝜ᛶᑐ↷⣽⬊࡜࡞ࡿࣄࢺ஧ಸయ
⣽⬊ࡢධᡭ࡜฼⏝ࡢྍ⬟ᛶࢆ຺᱌ࡋ࡚ࠊࡑࡢタᐃࡢྍྰࢆ᳨ウࡍࡿࠋ㸫㸫ᮏヨ㦂ࡣ࠶ࡃࡲ࡛ࠊ୰㛫〇ရཪࡣ᭱⤊〇ရ࡟࠾ࡅࡿ㐀⭘⒆ᛶ⣽⬊ࡢΰᅾࡢ᭷↓ࢆホ౯ࡍࡿࡶࡢ࡛࠶ࡗ࡚ࠊࣄࢺ࡛ࡢ⭘⒆໬ࢆ┤᥋ホ౯ࡍࡿヨ㦂࡛ࡣ࡞࠸ࡇ࡜ࢆㄆ㆑ࡋ࡚࠾ࡃᚲせࡀ࠶ࡿࠋࡲࡓୖグࡣࠊ᭱ࡶཝᐦ࡟〇ရ୰ࡢᙧ㉁㌿᥮⣽⬊ࡢΰᅾࢆホ౯ࡍࡿሙྜࡢ౛࡛࠶ࡿࠋinvivo ヨ㦂ࡣ in vitro ヨ㦂ࡢ⤖ᯝࢆ༑ศ㋃ࡲ࠼ࡓୖ࡛ィ⏬ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ in vitro ヨ㦂࡛ࡢ⤖ᯝࢆ㋃ࡲ࠼ࡓୖ࡛ࠊᛕࡢࡓࡵࠊin vivo ࡛☜ㄆࡋࡼ࠺࡜ࡍࡿሙྜ࡞࡝࡟ࡣࠊin vitro ヨ㦂࡛ࡢ᳨ฟឤᗘࠊ⢭ᗘ࡞࡝ࢆ⪃៖ࡋࠊ┠ⓗ࡟ἢ࠺ෆᐜ࡜⛬ᗘ࡛ࡶࡼ࠸ࠋ࡞࠾ࠊᙧ㉁㌿᥮⣽⬊ࡢ㐀⭘⒆ᛶ࡟ᑐࡋ࡚⛣᳜㒊఩ࡢᚤᑠ⎔ቃࡀᙳ㡪ࢆ୚࠼ࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿ 20,21ࠋࡋࡓࡀࡗ࡚ࠊ
౛࠼ࡤ⫼㒊⓶ୗ⛣᳜ヨ㦂ࢆ⾜࠺ሙྜࠊ⓶ୗ⛣᳜௨እࡢᢞ୚࡛ࡢ⮫ᗋ౑⏝ࡀ᝿ᐃࡉࢀ࡚࠸ࡿ
〇ရ࡟ࡘ࠸࡚ࡣࠊ⫼㒊⓶ୗ⛣᳜࡛ࡣ⭘⒆ࢆᙧᡂࡋ࡞࠸ᙧ㉁㌿᥮⣽⬊ࡢᏑᅾࡢྍ⬟ᛶࢆ⪃៖ࡋࡓ࠺࠼࡛〇ရࡢࣜࢫࢡホ౯ࢆ⾜࠺ࡇ࡜ࠋࡶࡋᚓࡽࢀࢀࡤࠊ≉ᐃࡢࣄࢺࡀࢇ⣽⬊✀ࡢື≀యෆ࡬ࡢ⛣᳜ヨ㦂㸦PDX㸸 Patient-Derived Xenograft㸧࡟㛵ࡍࡿᩥ⊩᝟ሗ࡞࡝ࡶཧ⪃࡜ࡍࡿࠋ᭱⤊〇ရ⣽⬊ࡢࣄࢺ࡟࠾ࡅࡿ⏕╔㒊఩࡛ࡢ⭘⒆ᙧᡂ⬟ࢆホ౯ࡍࡿࡓࡵࡢヨ㦂᭱⤊〇ရࡢ㐀⭘⒆ᛶࢆホ౯ࡍࡿ࡟࠶ࡓࡗ࡚୺࡟ᚲせ࡞᝟ሗ࡜ࡋ࡚ࡣࠊ
ձᮍศ໬ࣄࢺ ES/iPS⣽⬊ࡢΰᅾ㔞ࠊղᙧ㉁㌿᥮⣽⬊ࡢΰᅾ㔞࡟ຍ࠼ࠊճ⏕╔㒊఩࡛ࡢᢞ୚⣽⬊ࡢ⭘⒆ᙧᡂ⬟ࠊࡀᣲࡆࡽࢀࡿࠋձࠊղ࡟ࡘ࠸࡚ࡣࠊከ⬟ᛶᖿ⣽⬊ࡢศᏊ࣐࣮࣮࢝ࡢ᳨ฟࠊ୙Ṛ໬⣽⬊ࡢ᳨ฟࡸ㊊ሙ㠀౫ᏑᛶቑṪ⣽⬊ࡢ᳨ฟ࡞࡝࡛ࡑࢀࡒࢀホ౯ࡀྍ⬟࡛࠶ࡿࠋࡲࡓࠊ5.2.1.2.ཬࡧ 5.2.2.2.
࡛♧ࡋࡓࡼ࠺࡞ in vivo ヨ㦂ࡶ⪃࠼ࡽࢀࡿࠋ୍᪉ࠊճ⏕╔㒊఩࡛ࡢᢞ୚⣽⬊ࡢ⭘⒆ᙧᡂ⬟࡟ࡘ࠸࡚ࡣ⏕╔㒊఩࡛ࡢ in vivo 㐀⭘⒆ᛶヨ㦂ࢆ⾜࠺௨እ࡟ホ౯᪉ἲࡣ࡞࠸ࠋࡑࡢሙྜ࡟⪃៖
ࡍ࡭ࡁⅬ࡜ࡋ࡚ࡣࠊa) ヨ㦂ື≀ࡢ㑅ᢥࠊb) ᑐ↷⣽⬊ࡢ㑅ᢥ࣭ヨ㦂⣔ࡢ᳨ฟ⬟ຊࠊc) ヨ㦂ື≀ࡢᩘࠊd) ヨ㦂᳨యࡢᢞ୚㒊఩࡜᳨య୰ࡢ⣽⬊ᩘཬࡧ᳨యࡢᙧែࠊe) ほᐹᮇ㛫ࠊf) ᢞ୚㒊఩ࡢほᐹࠊg) ᢞ୚㒊఩ࡢ⤌⧊Ꮫⓗホ౯ࠊᢞ୚ࣄࢺ⣽⬊ࡢྠᐃࡸ⏕╔ࡋ࡚࠸ࡓࡇ࡜ࡢ☜ㄆࠊศ໬ᗘࢆ♧ࡍ⤌⧊Ꮫⓗホ౯ࠊh) ⤖ᯝࡢゎ㔘ἲ࡞࡝ࡀᣲࡆࡽࢀࡿࠋ≉࡟ᢞ୚㒊఩ࡣࠊྍ⬟࡞⠊ᅖ࡛ࣄࢺ࡛ࡢᢞ୚㒊఩࡟┦ᙜࡍࡿ㒊఩ࢆ㑅ᢥࡍࡿࡇ࡜ࢆ⪃៖ࡍࡿࠋࡇࢀࡣࠊ⏕╔㒊఩ࡢᚤᑠ⎔ቃࡢ㐪࠸࡟ࡼࡗ࡚⭘⒆ᙧᡂ⬟ࡸࠊ⭘⒆ࡢࢱ࢖ࣉࡀ␗࡞ࡿ࠾ࡑࢀࡀ࠶ࡾ 20,21ࠊࣄࢺ࡬ࡢእ
ᤄᛶࢆ⪃࠼ࡿ࡜ࡁ࡟ၥ㢟࡜࡞ࡿྍ⬟ᛶࡀ࠶ࡿࡓࡵ࡛࠶ࡿࠋࡶࡋࠊ≀⌮ⓗ㞀ᐖࢆ⏕ࡎࡿ࡞࡝ࡢ
⌮⏤࡟ࡼࡾᙜヱ㒊఩࡟ᑐࡍࡿᢞ୚⣽⬊ᩘ࡟㝈⏺ࡀ࠶ࡿሙྜ࡟ࡣࠊྍ⬟࡛࠶ࢀࡤᢞ୚㒊఩ࢆኚ᭦ࡍࡿࡢ࡛ࡣ࡞ࡃࠊື≀࡜ࣄࢺ࡜ࡢ㛫ࡢᙜヱᢞ୚㒊఩ࡢ┦ᑐⓗࢫࢣ࣮ࣝẚ࡟ᛂࡌࡓᢞ୚
⣽⬊ᩘࡢㄪ⠇࡞࡝ࢆ᳨ウࡍࡿࠋࡍ࡞ࢃࡕࠊ⏕╔ࡍࡿᚤᑠ⎔ቃ࡜ᢞ୚⣽⬊࡜ࡢ┦஫స⏝࡟ࡼࡿ⭘⒆ᙧᡂࡢྍ⬟ᛶࢆ⪃ᐹࡍࡿࡇ࡜ࢆඃඛࡍࡿࠋච␿≉ᶒࠊ⅖⑕ࠊ⹫⾑࡞࡝ࠊ≉Ṧ࡞ᢞ୚⎔ቃ࡟࠾ࡅࡿ⣽⬊ࡢᣲືࡣࣔࢹࣝື≀࡟࠾ࡅࡿ in vivo ࡛ࡢヨ㦂ࡀព⩏ࡢ࠶ࡿ᝟ሗࢆᥦ౪ࡍࡿྍ
⬟ᛶࡀ㧗࠸࡜⪃࠼ࡽࢀࡿ࠿ࡽ࡛࠶ࡿࠋࡓࡔࡋࠊ๓⮫ᗋẁ㝵࡛ࡢヨ㦂⤖ᯝࡢࣄࢺ࡬ࡢእᤄᛶࢆ᳨ウࡍࡿ࡜ࡁ࡟ࡣࠊࣄࢺయෆᒁᡤᚤᑠ⎔ቃࢆᙧᡂࡍࡿᾮᛶᅉᏊࡸཷᐜయࢱࣥࣃࢡ㉁➼ࡢせ⣲ࡣࡑࢀࡒࢀ㧗࠸ࣄࢺ≉␗ᛶࢆ♧ࡋࠊ⏕╔㒊఩ࡢᚤᑠ⎔ቃࡀື≀࡟࠾࠸࡚࡝ࡢ⛬ᗘࣔࢹࣝ໬࡛ࡁ࡚࠸ࡿ࠿ࡀ୙࡛᫂࠶ࡿࡇ࡜࡟ࡶ␃ពࡍࡿࠋ
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ヨ㦂ື≀ࡢ㑅ᢥࣄࢺ⣽⬊ຍᕤ〇ရࢆᏳᐃⓗ࡟యෆ࡛⏕╔ࡉࡏࡿࡓࡵࡢච␿୙඲ື≀࡜ࡋ࡚ࡣࠊNOG ࣐࢘ࢫ 6ࠊNSG ࣐࢘ࢫ 7 ࡞࡝ࡢ㔜ᗘච␿୙඲࣐࢘ࢫ⣔⤫ࡀᣲࡆࡽࢀࡿࠋࡇࢀࡽࡢ࣐࢘ࢫࡣ T ⣽⬊ࠊB ⣽⬊ཬࡧ NK ⣽⬊ࢆḞኻࡋ࡚࠾ࡾࠊࢾ࣮ࢻ࣐࢘ࢫ࡜ẚ࡭࡚ࣄࢺࡢ⣽⬊ࡸ⤌⧊ࡢ⏕╔ᛶࡀ㧗࠸ 8,9,10ࠋBRG ࣐࢘ࢫࡶ T ⣽⬊ࠊB ⣽⬊ཬࡧ NK ⣽⬊ࢆḞኻࡋࡓ⣔⤫ࡔࡀࠊࣄࢺ㐀⾑ᖿ⣽⬊ࡢ⏕╔ᛶࡀ NOG ࣐࢘ࢫࡸ NSG ࣐࢘ࢫࡼࡾࡶప࠸ࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࡓࡵ 11,12ࠊ౑⏝᫬࡟ࡣ┠ⓗ࡞࡝ࢆ຺᱌ࡋ࡚㑅ᐃࡍࡿࡇ࡜ࡀᚲせ࡛࠶ࡿࠋT ⣽⬊࡜ B ⣽⬊ࢆḞኻࡋࡓ SCID ࣐࢘ࢫࡸ NOD/SCID ࣐࢘ࢫࡣࠊ㢖⦾࡟⬚⭢⭘ࢆ⮬↛Ⓨ⑕ࡍࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠾ࡾࠊ⤖ᯝࡢゎ㔘࡟ᙳ㡪ࢆ୚࠼ࡿᜍࢀࡀ࠶ࡿࡓࡵ౑⏝ࢆ᥎ዡࡋ࡞࠸ࠋ
࡞࠾ࠊ48 㐌㱋ᮍ‶ࡢ NOG ࣐࢘ࢫࡣ⭘⒆ࢆ⮬↛Ⓨ⑕ࡍࡿࡇ࡜ࡣ⛥࡛࠶ࡿ 22ࠋච␿≉ᶒࠊ⅖
⑕ࠊ⹫⾑࡞࡝≉Ṧ࡞ᢞ୚⎔ቃ࡟࠾ࡅࡿ⣽⬊ࡢᣲືࡀၥ㢟࡜࡞ࡿሙྜࡣࠊ⑌ᝈࣔࢹࣝື≀ࡢ౑⏝ࡶ⪃៖ࡍࡿࠋࡇࡢሙྜࠊ⑌ᝈࣔࢹࣝື≀ࡀ࡝ࢀࡔࡅ㐺ᛂ⑕࡜࡞ࡿ⑌⑓ࡢ⑓ែⓗ≉ᚩࢆ௦⾲ࡋ࡚࠸ࡿ࠿ࡢ஦๓ࡢ᳨ウࡶᚲせ࡜࡞ࡿࠋࡓࡔࡋࠊ᭷⏝ᛶࡀホ౯ࡉࢀࡓ⑌ᝈࣔࢹࣝື≀ࢆ⏝࠸ࡓヨ㦂⣔ࡣࠊ᭷ຠᛶࡢヨ㦂ホ౯࡟ࡣ᭷⏝࡛࠶ࡿࡀࠊච␿ᢚไ๣ࡢ㛗ᮇᢞ୚ࡀᚲせ࡛࠶ࡾࠊᏳ
ᐃࡋࡓ㛗ᮇ㛫ࡢヨ㦂⣔୍࡛ᐃࡢ⤫ィᏛⓗ⤖ㄽࢆฟࡍ㐀⭘⒆ᛶヨ㦂࡟ࡣホ౯ࡀ㞴ࡋࡃ୙ྥࡁ
࡞ሙྜࡀ࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊヨ㦂┠ⓗ➼ࡶ຺᱌ࡋ࡚⑌ᝈࣔࢹࣝື≀ࢆ᥇⏝ࡍࡿ࠿࡝࠺࠿ࢆỴᐃࡍ࡭ࡁ࡛࠶ࡿࠋᐇ㝿ࠊ๓㏙ࡢ⌮⏤࠿ࡽࠊ㐀⭘⒆ᛶヨ㦂࡟࠾࠸࡚ࡣࠊ⑌ᝈࣔࢹࣝື≀࡛ࡣ࡞ࡃࣄࢺ⣽⬊ࡢ⛣᳜ࡀᐜ᫆࡞ච␿୙඲ື≀ࢆ⏝࠸ࡿࡇ࡜ࡀከ࠸ࠋNOG ࡸ NSG ࡯࡝ච␿≧ែࡀᢚไࡉࢀ࡚࠸ࡿ⣔⤫ࡀ฼⏝ྍ⬟࡞ື≀✀ࡣ࣐࢘ࢫࡢ௚࡟ࡣ࡞࠸ࡀࠊ࣐࢘ࢫ࡛ࡣᢞ୚㒊఩ࡢࢧ࢖ࢬࡀᑠࡉࡍࡂࡿཪࡣ⑌ᝈࣔࢹࣝࢆస〇ࡍࡿࡇ࡜ࡀᅔ㞴࡞࡝ࡢၥ㢟ࡀ࠶ࡿࠋࡑࡢሙྜࠊ
T ⣽⬊ࡀḞኻࡋ࡚࠸ࡿࢾ࣮ࢻࣛࢵࢺ࡞࡝ࠊ࣐࢘ࢫࡼࡾࡶ኱ᆺࡢච␿ᢚไື≀ࡀ⏝࠸ࡽࢀࡿࡇ
࡜ࡀ࠶ࡿ 10,14,23ࠋࡉࡽ࡟኱ࡁ࡞ື≀ࡢሙྜࡣࠊᙉࡃච␿ࡀᢚไࡉࢀࡓಶయࢆධᡭࡍࡿࡇ࡜ࡀ
㞴ࡋ࠸ࡓࡵࠊච␿ᢚไ๣ࢆే⏝ࡍࡿࡇ࡜࡟࡞ࡿࡀࠊ▷ᮇࡢ࠺ࡕ࡟ຠຊࡸᛶ⬟ࢆ⿬௜ࡅࡿࢹ࣮
ࢱࢆᚓࡿヨ㦂࡟ࡣ฼⏝ྍ⬟࡛ࡶࠊ㐀⭘⒆ᛶヨ㦂ࡢࡼ࠺࡞᫬㛫ࢆせࡍࡿヨ㦂࡟ࡣ୙ྥࡁ࡛࠶
ࡿࠋᑐ↷⣽⬊ࡢ㑅ᢥච␿୙඲ື≀ࢆ⏝࠸ࡓ in vivo 㐀⭘⒆ᛶヨ㦂࡛ࡣࠊ〇ရ⣽⬊ཪࡣ㝜ᛶᑐ↷⣽⬊࡜࡞ࡿࣄࢺ
஧ಸయ⣽⬊࡟㝧ᛶᑐ↷⣽⬊ࢆࢫࣃ࢖ࢡࡋࡓ㝧ᛶᑐ↷⩌ࡀタࡅࡽࢀ࡚࠸ࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ
㝧ᛶᑐ↷⣽⬊ࡢ✀㢮ࡣࠊ〇ရ୰࡟ྵࡲࢀ࡚࠸ࡿ㐀⭘⒆ᛶ⣽⬊࡜ࡋ࡚ఱࢆ᝿ᐃࡍࡿ࠿࡟ࡼࡗ
࡚␗࡞ࡿࠋ〇ရ୰࡟ྵࡲࢀ࡚࠸ࡿ㐀⭘⒆ᛶ⣽⬊ࡢ≉ᛶࡀணࡵ᥎ᐃࡉࢀ࡚࠾ࡾࠊ࠿ࡘࡇࢀ࡟㢮ఝࡍࡿ⾲⌧ᆺࢆ♧ࡍ⣽⬊ᰴࡀ฼⏝ྍ⬟࡞ሙྜ࡟ࡣࠊࡑࡢ⣽⬊ᰴࢆ㑅ᢥࡍࡿࠋࡑࡢࡼ࠺࡞⣽⬊ᰴࡀ฼⏝ྍ⬟࡛࡞࠸ሙྜࡣࠊ⭘⒆ᙧᡂ⬟ࡀⰋࡃ◊✲ࡉࢀㄆ▱ࡉࢀ࡚࠸ࡿ HeLa ⣽⬊➼ࢆ㝧ᛶᑐ↷⣽⬊࡜ࡋ࡚౑⏝ࡍࡿࠋ࡞࠾ࠊ㝧ᛶᑐ↷⣽⬊࡟ࡣࠊ㐺ษ࡟ရ㉁⟶⌮ࡉࢀࡓ⣽⬊ᥦ౪ᶵ㛵࠿ࡽධᡭࡋࡓ⣽⬊ᰴࢆ౑⏝ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋ㝧ᛶᑐ↷⩌࡜ࡋ࡚㐀⭘⒆ᛶࢆ♧ࡍ୰㛫〇ရࢆ⏝࠸ࡿሙྜ࡟ࡣࠊᙜヱ୰㛫〇ရ୰ࡢ㐀⭘⒆ᛶ⣽⬊ࡢ㔞ࢆู㏵ࠊin vitro ヨ㦂ἲ➼࡟ࡼࡾ☜㸫㸫

ㄆࡍࡿࡇ࡜ࡀᚲせ࡛࠶ࡿࠋ㝧ᛶᑐ↷⩌ࡀタᐃ࡛ࡁ࡞࠸ሙྜ࡟ࡣࠊヨ㦂⤖ᯝࡀ㝜ᛶ࡛࠶ࡗ࡚ࡶ
┿ࡢ㝜ᛶ࡞ࡢ࠿ഇ㝜ᛶ࡞ࡢ࠿ࡢホ౯ࡀᅔ㞴࡟࡞ࡿⅬࠊࡘࡲࡾࠊᮇᚅࡍࡿᛶ⬟ࡢヨ㦂ࡀᐇ᪋࡛ࡁࡓࡢ࠿ࠊཬࡧヨ㦂⤖ᯝ࡟ࡼࡗ࡚࡝ࡢࡼ࠺࡞ホ౯ࡀྍ⬟࡛࠶ࡿࡢ࠿࡜࠸࠺Ⅼࢆㄝ᫂ࡍࡿᚲ
せࡀ⏕ࡌࡿࡇ࡜࡟␃ពࡋࠊ㐀⭘⒆ᛶヨ㦂ࡢᐇ᪋ࡢព⩏ࢆ᳨ウࡍࡿࠋ㝜ᛶᑐ↷⩌࡟ࡘ࠸࡚ࡣࠊ
㝜ᛶᑐ↷⣽⬊࡜࡞ࡿࣄࢺ஧ಸయ⣽⬊ࡢධᡭ࡜฼⏝ࡢྍ⬟ᛶࢆ຺᱌ࡋ࡚ࠊࡑࡢタᐃࡢྍྰࢆ
᳨ウࡍࡿࠋ
ᮍศ໬ ES/iPS ⣽⬊ࡣΰᅾࡏࡎࠊ୍᪉ࠊΰᅾࡀ᝿ᐃࡉࢀࡿᙧ㉁㌿᥮⣽⬊ࡢ≉ᚩࡀ᫂ࡽ࠿࡛ࠊ
㐺ษ࡞㝧ᛶᑐ↷ᙧ㉁㌿᥮⣽⬊ࡀ࠶ࡿሙྜࡣࠊࡑࡢホ౯ヨ㦂ࢆ⏕╔㒊఩࡛ᐇ᪋ࡋ࡚ TPD50ࠊ
TPDmin ཬࡧࡑࡢ⭘⒆᳨ฟᮇ㛫ࢆタᐃࡋࡓୖ࡛ࠊ〇ရ⣽⬊ࡢ⏕╔㒊఩࡬ࡢ⛣᳜ࢆᐇ᪋ࡍࡿࡇ࡜ࡀ⫢せ࡛࠶ࡿࡀࠊࡑࡢࡼ࠺࡞౛ࡣ⛥࡛࠶ࡿ࡜⪃࠼ࡽࢀࡿࠋ〇ရ୰࡟ྵࡲࢀ࡚࠸ࡿ㐀⭘⒆ᛶ
⣽⬊ࡢ≉ᛶࡀ஦๓࡟୙࡛᫂࠶ࡿሙྜ࡟ࡣࠊヨ㦂⤖ᯝࡢゎ㔘ࡣࠊ࠶ࡃࡲ࡛ΰᅾ㐀⭘⒆ᛶ⣽⬊ࡢ㐀⭘⒆ᛶࢆ㝧ᛶᑐ↷⣽⬊࡜ྠ➼࡜௬ᐃࡋࡓୖ࡛࡞ࡉࢀࡿࡶࡢ࡛࠶ࡿࡇ࡜࡟ὀពࡍࡿࡇ࡜ࠋ
ヨ㦂ື≀ࡢᩘ࡜ᛶู
ヨ㦂ື≀ࡢᩘࡣࠊ⛣᳜⾜Ⅽࡢ㞴᫆ᗘࡸヨ㦂ື≀ࡢ⏕Ꮡ⋡➼ࢆ⪃៖ࡋࡓୖ࡛タᐃࡍࡿࠋ㸯⩌࡟ࡘࡁ᭱⤊ホ౯ྍ⬟࡞༉ᩘ࡜ࡋ࡚ 10 ༉௨ୖ࡛ᐇ᪋ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࡀࠊ㸯⩌࡟ࡘࡁ᭱⤊ホ౯ྍ⬟࡞༉ᩘ࡜ࡋ࡚᭱ప࡛ࡶ 6 ༉௨ୖ࡛ᐇ᪋ࡍࢀࡤࠊᐃ㔞ⓗ ᐃ㡯┠࡟࠾ࡅࡿࢹ࣮ࢱࡢ
ࣂࣛࢶ࢟ࡀẕ㞟ᅋࡢࣂࣛࢶ࢟ࢆᴫࡡ཯ᫎࡋ࡚࠸ࡿ࡜⪃࠼ࡽࢀࡿࠋ㝧ᛶᑐ↷⩌ࡢ TPDmin ௨ୖࡢΰᅾࡀ࡞࠸ࡇ࡜ࢆ⤫ィᏛⓗ☜࠿ࡽࡋࡉ࡜࡜ࡶ࡟♧ࡍࡓࡵࡢ༉ᩘࡢタᐃ᪉ἲࡶ▱ࡽࢀ࡚࠸ࡿ 8ࠋ᭱⤊〇ရ⣽⬊ࡢࣄࢺ࡟࠾ࡅࡿ⏕╔㒊఩࡛ࡢ⭘⒆ᙧᡂ⬟ࢆホ౯ࡍࡿࡓࡵࡢヨ㦂࡛ࡣࠊཎ๎࡜ࡋ࡚㸯⩌࡟㞤㞝ࡢື≀ࡀྠᩘྵࡲࢀࡿࡼ࠺࡟ࡋࡓ᪉ࡀᛶᕪࡢᙳ㡪ホ౯ࡣ⾜࠸ࡸࡍࡃ࡞
ࡿࠋࡓࡔࡋࠊ⮫ᗋ㐺⏝ࡀ୍᪉ࡢᛶࡢࡳ࡟㝈ᐃࡉࢀ࡚࠸ࡿሙྜ➼ࠊᢞ୚〇ရࡢ⭘⒆ᙧᡂ⬟࡟࠾࠸࡚ᛶᕪࡢᙳ㡪ࡀ↓ど࡛ࡁࡿሙྜ࡟ࡣ∦ᛶ࡛ᐇ᪋ࡋ࡚ࡶᵓࢃ࡞࠸ࠋ
ヨ㦂᳨యࡢᢞ୚㒊఩࡜᳨య୰ࡢ⣽⬊ᩘཬࡧ᳨యࡢᙧែ
ື≀ࢆ⏝࠸ࡓపศᏊ་⸆ရࡢ㠀⮫ᗋᏳ඲ᛶヨ㦂࡟࠾ࡅࡿ᳨యᢞ୚㔞ࡣ୍⯡࡟ࠊ✀ᕪ࡜ಶయᕪࢆ⪃៖ࡋࡓ୙☜ᐇಀᩘ㸦Ᏻ඲ಀᩘ㸧ࢆຍ࿡ࡋࠊࣄࢺ࡬ࡢᢞ୚㔞௨ୖ࡟タᐃࡉࢀࡿࠋࡋ࠿
ࡋࠊࣄࢺ⣽⬊ຍᕤ〇ရࡢ in vivo 㐀⭘⒆ᛶヨ㦂ࡢሙྜࠊື≀ࡢࢧ࢖ࢬࡢไ⣙࠿ࡽࠊࣄࢺ࡬ࡢ
ᢞ୚㔞࡜ྠᩘཪࡣࡑࢀ௨ୖࡢᩘࡢ⣽⬊ࢆᢞ୚ࡍࡿࡇ࡜ࡀᅔ㞴࡞ሙྜࡀከ࠸ࠋࡶࡋࠊ≀⌮ⓗ㞀ᐖࢆ⏕ࡎࡿ࡞࡝ࡢ⌮⏤࡟ࡼࡾࠊࣄࢺ࡛ࡢᢞ୚᫬࡜ྠᵝࡢ㒊఩࡟ྠᵝࡢ⤒㊰࡛ᢞ୚ࡍࡿ⣽⬊ᩘ࡟㝈⏺ࡀ࠶ࡿሙྜ࡟ࡣࠊྍ⬟࡛࠶ࢀࡤᢞ୚㒊఩ࢆኚ᭦ࡍࡿࡢ࡛ࡣ࡞ࡃࠊື≀࡜ࣄࢺ࡜ࡢ㛫ࡢᙜヱᢞ୚㒊఩ࡢ┦ᑐⓗࢫࢣ࣮ࣝẚ࡟ᛂࡌࡓᢞ୚⣽⬊ᩘࡢㄪ⠇࡞࡝ࢆ⾜࠺ࠋࡍ࡞ࢃࡕࠊ⏕╔ࡍࡿᚤᑠ⎔ቃ࡜ᢞ୚⣽⬊࡜ࡢ┦஫స⏝࡟ࡼࡿ⭘⒆ᙧᡂࡢྍ⬟ᛶࢆ⪃ᐹࡍࡿࡇ࡜ࢆඃඛࡍࡿࠋ
┦ᑐⓗࢫࢣ࣮ࣝẚ࡜ࡋ࡚ࡣ㠃✚ẚࡸయ✚ẚ࡞࡝ࡀ⪃࠼ࡽࢀࡿࡀࠊ࡝ࡢẚ⋡ࢆ㑅ᢥࡍࡿ࠿ࡣࠊ
〇ရࡢᵓ㐀ࠊ๣ᙧࡸࠊࡑࡢ㐺⏝᪉ἲࡢ≉ᚩࢆࡶ࡜࡟〇ရࡈ࡜࡟ㄝ᫂ࡉࢀࡿ࡭ࡁࡶࡢ࡛࠶ࡿࠋ
㒊఩ࢆඃඛࡍࡿ⌮⏤ࡣࠊච␿≉ᶒࠊ⅖⑕ࠊ⹫⾑࡞࡝ࠊ≉Ṧ࡞ᢞ୚⎔ቃ࡟࠾ࡅࡿ⣽⬊ࡢᣲືࡣ㸫㸫

ࣔࢹࣝື≀࡟࠾ࡅࡿ in vivo ࡛ࡢホ౯࡛࡞ࡅࢀࡤࠊ⪃ᐹࡍࡿࡇ࡜ࡀᅔ㞴ࡔ࠿ࡽ࡛࠶ࡿࠋࡓࡔ
ࡋࠊࣄࢺ࡛ࡢᢞ୚㒊఩࡟┦ᙜࡍࡿ㒊఩࡬ࡢᢞ୚ࡀᢏ⾡ⓗ࡟ᅔ㞴࡞ሙྜࠊヨ㦂⤖ᯝࡢゎ㔘ࡀᅔ㞴࡛࠶ࡿሙྜࠊูࡢ㒊఩࡟ᢞ୚ࡍࡿ᪉ࡀᡭᢏࡸឤᗘ࡞࡝ࡢヨ㦂ᛶ⬟㠃࡛ඃࢀࡿࡇ࡜ࡀ᫂ࡽ
࠿࡞ሙྜ࡞࡝ࠊྜ⌮ⓗ࡟ጇᙜᛶࡀㄝ࡛᫂ࡁࡿሙྜ࡟ࡣࡇࡢ㝈ࡾ࡛ࡣ࡞࠸ࠋᢞ୚᳨యࡢᙧែࡣࠊ
ྍ⬟࡛࠶ࢀࡤ᭱⤊〇ရࡢᵓ㐀ཪࡣ๣ᙧ࡜ྠᵝࡢࡶࡢ࡜ࡍࡿࠋ
ほᐹᮇ㛫ྛ⩌ࡢ඲౛࡟ࡘ࠸࡚ࠊ୍⯡≧ែࢆẖ᪥ほᐹࡋࠊ㐌㸯ᅇ௨ୖࡢ㢖ᗘ࡛య㔜 ᐃࡍࡿ࡜ྠ᫬࡟
〇ရ⣽⬊ࡀᢞ୚ࡉࢀࡓ㒊఩ࡢ⭘⒆ᙧᡂࡢ᭷↓ࡢ☜ㄆࢆࠊほᐹࡸゐデࠊ⏬ീデ᩿࡞࡝ࡢ᪉ἲ࡟
ࡼࡾᐇ᪋ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋࡓࡔࡋࠊᐇ㝿ࡢほᐹ㢖ᗘཬࡧ☜ㄆ㡯┠ࡣࠊ⛣᳜㒊఩ࠊ㯞㓉ࡸ᧜ീ᫬㛫࡞࡝ࡢື≀࡬ࡢ㈇Ⲵࢆ⪃៖ࡋࡓୖ࡛タᐃࡍࡿࡇ࡜ࠋほᐹᮇ㛫ࡢ㛗ࡉࡣࠊ㝧ᛶᑐ↷⩌ࡢ᭷↓ࡸ⛣᳜⣽⬊ཬࡧࡑࡢศ⿣࡟ࡼࡾ⏕ࡌࡓ⣽⬊ࡢయෆ࡛ࡢ᥎ᐃ⏕Ꮡᮇ㛫࡞࡝࡟ࡼࡗ࡚␗
࡞ࡿࠋ㝧ᛶᑐ↷⣽⬊ࢆ᭱⤊〇ရཪࡣྠࡌ⣽⬊✀ࡢṇᖖ⣽⬊ࡢࡼ࠺࡞㝜ᛶᑐ↷⣽⬊࡟ࢫࣃ࢖ࢡࡋࡓ㝧ᛶᑐ↷⩌ࡢ࠶ࡿሙྜࡣࠊヨ㦂᫬ཪࡣ஦๓᳨ウ࡟࠾࠸࡚ࠊ㝧ᛶᑐ↷⩌ࡢ୰࡛⭘⒆ᙧᡂ
ࡀㄆࡵࡽࢀࡿ TPDmin ࢆ☜ㄆࡍࡿࡇ࡜ࠋTPDmin ࡟࠾ࡅࡿ⭘⒆ᙧᡂ☜⋡ࡀ୍ᐃ್࡟㐩ࡍࡿ᫬Ⅼࢆ༑ศ㉸࠼ࡓ᫬Ⅼࡲ࡛ほᐹࡍࡿࡇ࡜࡟ࡼࡾࠊ㐀⭘⒆ᛶࡢ᭷↓ࢆุ᩿ࡍࡿࡇ࡜ࡀ࡛ࡁࡿࠋࡇࡢ
ሙྜࡢุ᩿ࡣࠊΰᅾࡋ࠺ࡿ㐀⭘⒆ᛶ⣽⬊ࡢ㐀⭘⒆ᛶࡀ㝧ᛶᑐ↷⣽⬊࡜ྠ➼࡛࠶ࡾࠊ⭘⒆ᙧᡂ
࡟ᚲせ࡞᭱ప⏝㔞ࡀ TPDmin ࡛࠶ࡿ࡜௬ᐃࡋࡓୖ࡛ࡢࡶࡢ࡜࡞ࡿࠋNOG ࣐࢘ࢫ࡟⓶ୗᢞ୚ࡋࡓሙྜ࡟ࡣࠊࣄࢺ iPS ⣽⬊ࡸ HeLa ⣽⬊ࡢ⭘⒆ᙧᡂ⋡ࡣࠊ4㹼6 ࠿᭶࡛࡯ࡰᏳᐃ࡟࡞ࡿࡇ࡜ࡀ
▱ࡽࢀ࡚࠸ࡿࡀ 8,10,13,14ࠊᡭᢏࡸ⣽⬊ࡢྲྀࡾᢅ࠸ࠊᇵ㣴ᒚṔ࡞࡝࡟ࡼࡾࠊ⭘⒆ᙧᡂ⋡ࡀᏳᐃࡍࡿࡲ࡛࡟せࡍࡿ᫬㛫ࡣࡤࡽࡘࡃࡢ࡛ࠊTPDmin ࡟࠾ࡅࡿ⭘⒆ᙧᡂ☜⋡ࡀ୍ᐃ್࡟㐩ࡍࡿࡲ࡛ࡢᮇ㛫ࡣࠊヨ㦂᪋タ࡟࠾࠸࡚☜ㄆࡍࡿᚲせࡀ࠶ࡿࠋ㝧ᛶᑐ↷⩌ࡀ࠶ࡿሙྜ࡛ࡶࠊ᭱⤊〇ရ୰ࡢ⣽⬊ࡢ㑇ఏⓗᏳᐃᛶࡀప࠸ࡇ࡜ࡀ᫂ࡽ࠿࡞ሙ
ྜ࡞࡝ࠊᢞ୚ᚋ࡟⏕╔㒊఩࡟࠾࠸࡚ᢞ୚ࡉࢀࡓ⣽⬊ࡀᙧ㉁㌿᥮ࡍࡿࡇ࡜࡟ࡼࡾ⭘⒆ࡀᙧᡂ
ࡉࢀࡿࡇ࡜ࡀᙉࡃᠱᛕࡉࢀࡿሙྜ࡟ࡣࠊࡼࡾ㛗ᮇࡢほᐹࡀᚲせ࡟࡞ࡿ࡜⪃࠼ࡽࢀࡿࠋࡓࡔࡋࠊ
ື≀ࡢᑑ࿨ࡶ࠶ࡾࠊほᐹࡢᘏ㛗࡟ࡶ㝈⏺ࡀ࠶ࡿ 24ࠋࡋࡓࡀࡗ࡚ࠊࡼࡾ㛗ᮇࡢほᐹ࡟ࡼࡗ࡚ࡶ
⭘⒆ᙧᡂࡀㄆࡵࡽࢀ࡞࠿ࡗࡓ࡜ࡋ࡚ࡶࠊ⮫ᗋᢞ୚ᚋࡢᙧ㉁㌿᥮࡟ࡼࡿ⭘⒆ᙧᡂࡢྍ⬟ᛶ࡟ࡘ࠸࡚ࡣࠊ౛࠼ࡤࣇ࢛࣮ࣟ࢔ࢵࣉཬࡧእ⛉ⓗษ㝖ࡸ⸆๣἞⒪࡞࡝࡟ࡼࡿࣜࢫࢡ࣐ࢿࢪ࣓ࣥ
ࢺࡢࣉࣛࣥࢆணࡵㅮࡌ࡚࠾ࡃࡇ࡜ࡀ㔜せ࡛࠶ࡿࠋ㝧ᛶᑐ↷⩌ࡢタᐃࢆࡏࡎ࡟ヨ㦂ࡍࡿሙྜࡣࠊ᭱⤊〇ရ⣽⬊ࡢᢞ୚ᚋ࠿ࡽື≀ࡀṚஸࡍࡿࡲ࡛ࡢᮇ㛫ࠊ⮬↛Ⓨ⏕⑓ኚࡸᑑ࿨ࡀホ౯࡟ᙳ㡪ࢆ୚࠼࡞࠸᭱㛗ᮇ㛫ཪࡣ⛣᳜⣽⬊ཬࡧࡑࡢศ⿣࡟ࡼࡾ⏕ࡌࡓ⣽⬊ࡀ☜ㄆ࡛ࡁ࡞ࡃ࡞ࡿࡲ࡛ࡢᮇ㛫ࠊ⭘⒆ᙧᡂࡢ᭷↓ࢆほᐹࡍࡿࡇ࡜ࡀ
ᮃࡲࡋ࠸ࠋ㝧ᛶᑐ↷⩌ࡢ᭷↓ࡢ௚࡟ࠊື≀✀ࠊ⣔⤫ࠊ⑓ែࠊච␿ᢚไ≧ែ࡞࡝ࡶ຺᱌ࡋࠊྜ⌮ⓗ࡟ㄝ᫂ྍ⬟࡞ほᐹᮇ㛫ࢆタᐃࡍࡿࡇ࡜ࠋ

㸫㸫

ᢞ୚㒊఩ࡢほᐹᢞ୚㒊఩࡟⭘⒗ࡢᙧᡂࡀ☜ㄆࡉࢀࡓሙྜ࡟ࡣࠊࡑࡢ᳨ฟ᪥ࢆグ㍕ࡍࡿࠋ⓶ୗ➼ࡢእほ࡟ࡼࡾ⭘⒗ᙧᡂࡢ☜ㄆࡀྍ⬟࡞ሙྜࡣࠊࡑࡢ▷ᚄ࡜㛗ᚄࢆ᭱ప 1 㐌㛫࡟ 1 ᅇࡢ㢖ᗘ࡛ ᐃࡋࠊ⭘⒗ࡢᡂ㛗ࢆホ౯ࡍࡿࡇ࡜ࡀᮃࡲࡋ࠸ࠋࡓࡔࡋࠊᐇ㝿ࡢ ᐃࡣࠊ㯞㓉ࡸ ᐃ᫬㛫࡞࡝ࡢື≀࡬ࡢ㈇Ⲵࢆ⪃៖ࡋࡓୖ࡛ィ⏬ࡋࠊᐇ᪋ࡍࡿࠋ
⭘⒗ࡢᡂ㛗ࡀ㐣ᗘ࡞ሙྜ࡟ࡣࠊື≀⚟♴ࡢほⅬ࠿ࡽࠊື≀ࢆᐃࡵࡽࢀࡓ᪉ἲ࡟ࡼࡾᏳᴦṚࡉࡏࡿࠋ⭘⒗ࡢ㏥⦰ࡀㄆࡵࡽࢀࡿሙྜ࡟ࡣࠊᐃࡵࡽࢀࡓほᐹᮇ㛫⤊஢ࡲ࡛ࡣᏳᴦṚࡉࡏ࡞࠸ࡇ࡜ࠋ⭘⒗ࡢᡂ㛗ࡀㄆࡵࡽࢀ࡞࠸ሙྜ࡟ࡣࠊ༶ᗙ࡟⭘⒆࡜ࡣุ᩿ࡋ࡞࠸ࡇ࡜ࠋ
⑓⌮Ꮫⓗホ౯ほᐹᮇ㛫⤊஢᫬࡟ࠊࡍ࡭࡚ࡢື≀ࢆᏳᴦṚࡉࡏࠊᢞ୚㒊఩ཬࡧᙧᡂࡉࢀࡓ⭘⒗࡟ࡘ࠸࡚๗
᳨ࢆ⾜࠺ࠋ⫗║ⓗ࡟ㄆࡵࡽࢀࡓ⭘⒗⤌⧊࡟ຍ࠼࡚⾑ὶࡀ㇏ᐩ࡞୺せ⮚ჾ㸦⫢⮚ࠊ⭁⮚ࠊ⭈⮚ࠊ⫵ࠊࣜࣥࣃ⠇࡞࡝㸧ࢆ᦬ฟࡋࠊ⭘⒗⤌⧊࡟ࡘ࠸࡚ࡣࠊHE ᰁⰍࡸච␿ᰁⰍ➼࡛ࠊࣄࢺ⏤᮶⣽⬊ࡀ࡝ࡢࡼ࠺࡞⤌⧊ࡢ⭘⒆ࢆᙧᡂࡋࡓ࠿☜ㄆࡍࡿࠋࡲࡓࠊ᦬ฟࡋࡓ௚ࡢ⮚ჾ࡟ࡘ࠸࡚ࡣ┠ど࡛⭘⒗ࡢ᭷↓ࢆ☜ㄆࡍࡿࠋࣄࢺ⣽⬊ࡢᾐ₶࣭㐲㝸㌿⛣ࡀ࡞࠸࠿ࢆࠊࣄࢺ⣽⬊㑇ఏᏊ࡟≉␗ⓗ࡞ Alu 㓄ิ࡟╔┠ࡋࡓ Alu PCR25,26 ࡸᢠࣄࢺ HLA ᢠయ➼ࢆ⏝࠸ࡓච␿ᰁⰍ➼࡛ホ౯ࡍࡿࡇ࡜ࡶ᭷⏝࡛࠶ࡿࠋࡇࡢ㝿࡟ࡣࠊホ౯᪉ἲࡢᛶ⬟㸦౛࠼ࡤឤᗘࡸ≉␗ᛶ࡞࡝㸧ࡣ஦๓࡟☜ㄆࡋ࡚࠾ࡃᚲせࡀ࠶ࡿࠋ᦬ฟࡋࡓ⤌⧊ࡣ඲࡚ಖᏑࡍࡿࠋ୍᪉ࠊほᐹᮇ㛫୰࡟⭘⒗ࡀほᐹࡉࢀ࡞࠿
ࡗࡓሙྜ࡛ࡶࠊഇ㝜ᛶࡢุᐃࢆ㜵ࡄࡓࡵࠊ⛣᳜ࡋࡓ⣽⬊〇ရࢆ᦬ฟࡋ⛣᳜ࡋࡓࣄࢺ⣽⬊ࡢ⤌⧊ീࢆ᳨ウࡍࡿࠋࡑࡢ㝿ࠊ⑓⌮⤌⧊Ꮫⓗ᳨ᰝ࡟ࡼࡗ࡚ࠊ⛣᳜⣽⬊ࡀ⛣᳜∦᦬ฟ๓ࡲ࡛⏕Ꮡࡋ࡚࠸ࡓࡇ࡜ࠊ⭘⒆ᙧᡂ⬟ࡀ࡞࠸ࡇ࡜ࠊཬࡧ〇ရࡢ౑⏝┠ⓗ࡟㐺ࡗࡓ⤌⧊ീ࡛࠶ࡿࡇ࡜ࢆ㐺ษ࡞ච␿ᰁⰍἲࡢ⤌ࡳ࠶ࢃࡏ࡛ド᫂ࡍࡿࡇ࡜ࡀ⫢せ࡛࠶ࡿࠋ࡞࠾ࠊ๓㏙࡜ྠᵝ࡟ࠊ⾑ὶࡀ㇏ᐩ࡞୺せ⮚ჾ㸦౛࠼ࡤ⫢⮚ࠊ⭁⮚ࠊ⭈⮚ࠊ⫵ࠊࣜࣥࣃ⠇࡞࡝㸧ࢆ᦬ฟࡋࠊᚋ᪥ᚲせ࡜࡞ࡿゎᯒࡢࡓࡵಖᏑࡋ࡚࠾ࡃࠋ
⤖ᯝࡢゎ㔘〇ရ⣽⬊ᢞ୚⩌࡟࠾࠸࡚⭘⒆ᙧᡂࡀㄆࡵࡽࢀࡓሙྜ࡟ࡣࠊ⭘⒆ࢆᵓᡂࡍࡿ⣽⬊ࡀࣄࢺ⏤᮶ࡢ⣽⬊࡛࠶ࡿ࠿ྰ࠿࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡍࡿ࡜࡜ࡶ࡟ࠊ〇ရ୰ࡢ㐀⭘⒆ᛶ⣽⬊ࡢΰᅾ㔞ࢆ☜ㄆࡋࡘࡘࠊ〇ရࡢ〇ἲࡸရ㉁つ᱁ࡢኚ᭦ࢆ᳨ウࡍࡿࡇ࡜ࠋ〇ရ⣽⬊ᢞ୚⩌࡟࠾࠸࡚⭘⒆ᙧ
ᡂࡀㄆࡵࡽࢀ࡞࠿ࡗࡓሙྜ࡟ࡣࠊഇ㝜ᛶࡢྍ⬟ᛶ࡟ࡘ࠸࡚ࠊ㝧ᛶᑐ↷⣽⬊ࡢ TPDmin ್࡞࡝࠿ࡽ⪃࠼ࡽࢀࡿ in vivo 㐀⭘⒆ᛶヨ㦂ࡢᛶ⬟ࢆ㋃ࡲ࠼࡚⪃ᐹࡍࡿ 8ࠋࡀࢇ⣽⬊࡞࡝ࡢ㐀⭘⒆ᛶ
ᙧ㉁㌿᥮⣽⬊ࡣከᵝᛶ࡟ᐩࡳࠊin vivo 㐀⭘⒆ᛶヨ㦂࡛ࡣ᳨ฟࡉࢀ࡟ࡃ࠸⣽⬊✀ࡀ࠶ࡿྍ⬟ᛶࡀ࠶ࡿࠋࡋࡓࡀࡗ࡚ࠊࡶࡋᚓࡽࢀࢀࡤࠊ≉ᐃࡢࣄࢺࡀࢇ⣽⬊✀ࡢື≀యෆ࡬ࡢ⛣᳜ヨ㦂㸦PDX㸸Patient-Derived Xenograft㸧࡟㛵ࡍࡿᩥ⊩᝟ሗ࡞࡝ࡶཧ⪃࡜ࡍࡿࠋヨ㦂⤖ᯝࡢゎ㔘ࡣࠊ࠶ࡃࡲ࡛ΰᅾ㐀⭘⒆ᛶ⣽⬊ࡢ㐀⭘⒆ᛶࢆ㝧ᛶᑐ↷⣽⬊࡜ྠ➼࡜௬ᐃࡋࡓୖ࡛࡞ࡉࢀࡿࡶࡢ
࡛࠶ࡿࡇ࡜࡟␃ពࡍࡿࡇ࡜ࠋ

㸫㸫

㸴㸬ࣄࢺయ⣽⬊㸭యᛶᖿ⣽⬊ຍᕤ〇ရࡢࡓࡵࡢ㐀⭘⒆ᛶ㛵㐃ヨ㦂ཎᩱ࣭ཎᮦᩱࡢရ㉁≉ᛶホ౯࣭ရ㉁⟶⌮ࡢࡓࡵࡢ㐀⭘⒆ᛶヨ㦂ࣄࢺయ⣽⬊㸭యᛶᖿ⣽⬊ຍᕤ〇ရࢆ〇㐀ࡍࡿࡓࡵࡢ⣽⬊ᇶᮦ㸦ཎᩱཪࡣཎᮦᩱ㸧࡜ࡋ࡚ࣄࢺయ⣽⬊ཪࡣࣄࢺయᛶᖿ⣽⬊ࡢࢭ࣭ࣝࣂࣥࢡࢆᶞ❧ࡋࡓ㝿࡟ࠊࡑࡢရ㉁≉ᛶホ౯ࢆ┠ⓗ࡜ࡋ࡚㐀⭘⒆ᛶヨ㦂ࢆ⾜࠺ሙྜ࡟ࡣࠊWHO TRS 978 ࡢ Annex 31 ࢆཧ⪃࡟ࡍࡿࡇ࡜ࠋ
᭱⤊〇ရࡢࡓࡵࡢ㐀⭘⒆ᛶ㛵㐃ヨ㦂ࡢ␃ពⅬ᭱⤊〇ရ࡜ࡋ࡚ࡢࣄࢺయ⣽⬊㸭యᛶᖿ⣽⬊ຍᕤ〇ရࡢ㐀⭘⒆ᛶ࡟㛵ࡋ࡚ࡣࠊᙧ㉁㌿᥮⣽⬊ࡢΰᅾ㔞࡜ࠊ⏕╔㒊఩࡛ࡢᢞ୚⣽⬊ࡢ⭘⒆ᙧᡂ⬟࡟ࡘ࠸࡚ࠊヨ㦂ࢹ࣮ࢱཪࡣᩥ⊩➼ࡢ᝟ሗࢆࡶ࡜࡟᳨ウࡍࡿᚲせࡀ࠶ࡿࠋ
᪤࡟ୡ⏺ྛᆅ࡛ࣄࢺ⣽⬊ࡢ⛣᳜་⒪ࡸࣄࢺయ⣽⬊㸭యᛶᖿ⣽⬊ຍᕤ〇ရࡢ⮫ᗋᛂ⏝ࡀ㐍ࢇ࡛࠸ࡿࠋࡋ࠿ࡋࠊࡇࢀࡽࡢ⣽⬊⛣᳜ࡸ〇ရᢞ୚ࡀཎᅉ࡜࡞ࡾ⭘⒆ࡀᙧᡂࡉࢀࡓࡇ࡜ࢆ♧ࡍ⑕౛ሗ࿌ࡣࠊࣄࢺ⫾ඣ⏤᮶ᇵ㣴⚄⤒ᖿ⣽⬊ࢆ⏝࠸ࡓẟ⣽⾑⟶ᣑᙇᛶ㐠ືኻㄪ⑕ࡢ἞⒪࡟ࡼࡾ⬻࡟Ⰻᛶࡢ⭘⒆ࡀᙧᡂࡉࢀࡓ࡜࠸࠺ሗ࿌ 27ࠊ⬨㧊ᦆയ἞⒪ࢆ┠ⓗ࡜ࡋࡓ⮬ᕫ⏤᮶Ⴅ⢓⭷㸦⣽⬊ࡢຍᕤ࡞ࡋ㸧ࢆ⛣᳜ࡋࡓᚋࡢ⭘⒗ᙧᡂ஦౛ 28ࠊ࠸ࢃࡺࡿࠕᖿ⣽⬊ࢶ࣮ࣜࢬ࣒ࠖࡢ୍⎔࡜ࡋ࡚ࢡࣜࢽࢵࢡ࡛㛫ⴥ⣔ᖿ⣽⬊ࠊES ⣽⬊ཬࡧ⫾ඣ⏤᮶⚄⤒ᖿ⣽⬊ࡢ㧊⭍ෆᢞ୚ࢆཷࡅࡓ
࡜ࡉࢀࡿ⹫⾑ᛶ⬻༞୰ᝈ⪅ࡢ⬨㧊࡟࠾ࡅࡿ⭘⒆ᙧᡂ஦౛ 29 ࡞࡝㝈ࡽࢀࡓࡶࡢࡋ࠿࡞࠸ࠋ࡞
࠾ࠊ㠀ᖖ࡟⛥࡛ࡣ࠶ࡿࡀࠊࢻࢼ࣮࡟࠾ࡅࡿ⾑ᾮ⭘⒆ࣜࢫࢡࡢୖ᪼ࡀㄆࡵࡽࢀ࡞࠸࡟ࡶ࠿࠿ࢃ
ࡽࡎࠊྠ✀⏤᮶㐀⾑ᖿ⣽⬊⛣᳜ᚋ࡟ᝈ⪅ࡀࢻࢼ࣮ࡢ⣽⬊࡟㉳ᅉࡍࡿⓑ⾑⑓ࢆⓎ⑕ࡍࡿࡇ࡜
ࡀ࠶ࡿࡇ࡜ࡶ▱ࡽࢀ࡚࠸ࡿ 30ࠋ෌⏕་⒪࣭⣽⬊἞⒪࡟ỗ⏝ࡉࢀࡿࣄࢺ㛫ⴥ⣔ᖿ⣽⬊ࢆཎᩱ࡜ࡋࡓ〇ရ࡟㝈ࢀࡤࠊ⮫ᗋ࡛ࡢ༢⊂ᢞ୚࡟ࡼࡿ⭘⒆ᙧᡂࡢሗ࿌ࡣᏑᅾࡋ࡞࠸ࠋ㐣ཤ࡟ࣄࢺ㛫ⴥ⣔ᖿ⣽⬊ࡢ in vitro ᇵ㣴᫬ࡢᝏᛶᙧ㉁㌿᥮ࡀ㸲௳ሗ࿌ࡉࢀ࡚࠸ࡿࡀࠊࡇࡢ࠺ࡕ 2 ௳ 31,32 ࡣࡀࢇ⣽⬊ᰴࡢࢡࣟࢫࢥࣥࢱ࣑ࢿ࣮ࢩࣙࣥ࡟ࡼࡿࡶࡢ࡛࠶ࡿࡇ࡜ࡀᚋ࡟ุ᫂ࡋ࡚࠸ࡿࠋࡲࡓࠊṧࡾࡢ㸰௳ 33,34 ࡛ࡣ in vitro ᇵ㣴᫬࡟⣽⬊ࡢ୙Ṛ໬ࡀ☜ㄆࡉࢀ࡚࠸ࡿࠋࡇࢀࡽࡢࡇ࡜ࡣࠊ᭱⤊〇ရ࡬ࡢ㐀⭘⒆ᛶ⣽⬊ࡢࢡࣟࢫࢥࣥࢱ࣑ࢿ࣮ࢩࣙࣥ㜵Ṇཬࡧ⣽⬊ቑṪ≉ᛶࡢᢕᥱࡀ㔜せ࡛࠶ࡿࡇ࡜ࢆ♧ࡋ࡚࠸ࡿࠋࡋࡓࡀࡗ࡚ࠊGCTP ┬௧࡟‽ᣐࡋࡓᕤ⛬⟶⌮ࡢୗ࡟ᇵ㣴࣭ຍᕤࡉࢀࠊ
᪤ᐃࡢᇵ㣴ᮇ㛫ࢆ㉸࠼ࡓ⣽⬊ࡢቑṪ≉ᛶゎᯒ࡛␗ᖖࡀ࡞࠸ࡇ࡜ࢆ☜ㄆࡋࡓࣄࢺయ⣽⬊㸭㛫ⴥ⣔ᖿ⣽⬊ຍᕤ〇ရ࡟ࡘ࠸࡚ࡣࠊ୍⯡ⓗ࡟ࡣච␿୙඲ື≀ࢆ⏝࠸ࡓ in vivo 㐀⭘⒆ᛶヨ㦂ࢆ⾜࠺ᚲせࡣ࡞࠸ࠋ
ࡓࡔࡋࠊձ᭱⤊〇ရ୰ࡢ⣽⬊ࡢቑṪᛶࡸᮍศ໬ᗘࡀ㧗࠸ࠊ㐣ཤ࡟⭘⒆ᙧᡂࡀሗ࿌ࡉࢀࡓ〇ရ࡟ྵࡲࢀ࡚࠸ࡓ⣽⬊✀ⱝࡋࡃࡣࡑࢀ࡜ྠᵝࡢ⣽⬊ࡀᢞ୚〇ရ୰࡟ྵࡲࢀࡿ࡞࡝ࡢ⌮⏤࡟ࡼࡾᢞ୚ᚋ࡟⏕╔㒊఩࡟࠾࠸࡚⭘⒆ࡀᙧᡂࡉࢀࡿࡇ࡜ࡀ㠀ᖖ࡟ᙉࡃᠱᛕࡉࢀࡿሙྜࠊղ᭱
⤊〇ရࢆ㠀┦ྠⓗ࡟౑⏝ࡍࡿሙྜࠊཪࡣճඹ㏻ࡢࣄࢺ⏤᮶ࡢཎᩱ⣽⬊࠿ࡽ〇㐀ࡉࢀࡓ〇ရࡀከࡃࡢᝈ⪅࡟ᢞ୚ࡉࢀࡿࡇ࡜࡟ࡼࡾ⭘⒆ᙧᡂࣜࢫࢡࡀᣑᩓࡍࡿ࠾ࡑࢀࡀ࠶ࡿሙྜ࡟ࡣࠊ
᪤ᐃࡢᇵ㣴ᮇ㛫ࢆ㉸࠼ࡓ⣽⬊ࡢቑṪ≉ᛶゎᯒ➼ࡢヨ㦂࡟ຍ࠼ࠊච␿୙඲ື≀ࢆ⏝࠸࡚ୖグ㸫㸫 㡯࡜ྠᵝࡢ㐀⭘⒆ᛶヨ㦂ࡢᐇ᪋ࢆ᳨ウࡍࡿࡇ࡜ࠋ
㸵㸬㑇ఏⓗᏳᐃᛶ࡟㛵ࡍࡿ୍⯡ⓗ␃ពⅬ㑇ఏⓗᏳᐃᛶࡢపୗࡣࠊ᰾ᆺ␗ᖖࡸ㑇ఏᏊኚ␗ࡢⓎ⏕☜⋡ࢆୖ᪼ࡉࡏࡿࡇ࡜ࢆ㏻ࡌ࡚ᙧ
㉁㌿᥮⣽⬊ࡢⓎ⏕☜⋡ࢆୖ᪼ࡉࡏࡿ࡜᥎ᐃࡉࢀࡿࡇ࡜࠿ࡽࠊ㐀⭘⒆ᛶࣜࢫࢡ࡟㛵ࡍࡿ₯ᅾⓗࣁࢨ࣮ࢻ࡛࠶ࡿࠋ
ࣄࢺ⣽⬊࡛ࡣࠊᇵ㣴࡟ࡼࡾ᰾ᆺኚ໬࡞࡝ࡢ㑇ఏᏊኚ␗ࡀ⏕ࡌࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࠋ᰾ᆺ
ࡀᏳᐃࡋ࡚࠸ࡿࣄࢺ஧ಸయ⥺⥔ⱆ⣽⬊࡛ࡉ࠼ࡶ୍ሷᇶ㑇ఏᏊከᆺ㸦௨ୗࠕSNPࠖ࡜࠸࠺ࠋ㸧࢔ࣞ࢖࡟ࡼࡿゎᯒ࡛ࡣⱝᖸࡢኚ␗ࢆ♧ࡋࠊࡲࡓࠊ㠀஧ಸయࡢ᰾ᆺࡀࠊ᫂ࡽ࠿࡞ṇᖖ⤌⧊࡟࠾࠸࡚ࡶ᫬ࠎほᐹࡉࢀࡿࡇ࡜ࡀ࠶ࡿࠋin vitro ࡛ほᐹࡉࢀࡿ᰾ᆺ␗ᖖ⣽⬊࡞࡝㑇ఏᏊኚ␗ࢆᣢ
ࡘ⣽⬊ࡢᏳ඲ᛶ࡟㛵ࡋ࡚ࡣࡲࡔ⤖ㄽࡣฟ࡚࠸࡞࠸ࠋ㑇ఏⓗᏳᐃᛶࡢ࣮࣋ࢫࣛ࢖ࣥ࡜࡞ࡿ㑇ఏᏊ᝟ሗࡣࠊ⣽⬊✀ࡸᇵ㣴᪉ἲ࡟ࡼࡗ࡚␗࡞ࡿࠋ⥅௦ᇵ㣴࡟࠾࠸࡚㑇ఏᏊ」〇ࡢ⤯ᑐⓗᏳᐃᛶࢆ♧ࡍ⣽⬊ࡣ↓࠸ࠋࡋࡓࡀࡗ࡚ࠊࣁࢨ࣮ࢻ࡛࠶ࡿ㑇ఏⓗ୙Ᏻᐃᛶࢆ᭱ᑠ㝈࡟ࡍࡿࡓࡵᇵ㣴ᮇ㛫ཬࡧ⥅௦ᅇᩘࢆไ㝈ࡋࠊᇵ㣴᮲௳ࡢ᪉ἲࡸኚ᭦ࡢᙳ㡪࡟ᑐࡍࡿࣜࢫࢡホ౯ࢆ⾜࠺࡭ࡁ࡛࠶ࡿࠋ㑇ఏⓗᏳᐃᛶヨ㦂ἲ࡜ࡋ࡚ࠊG ࣂࣥࢻ᰾ᆺゎᯒࠊFISHࠊ࢔ࣞ࢖ CGHࠊSNP ࢔ࣞ࢖ࠊḟୡ௦ࢩ࣮ࢡ࢚ࣥࢧ࣮࡞࡝࡟ࡼࡿゎᯒࡀᣲࡆࡽࢀࡿࠋG ࣂࣥࢻ᰾ᆺゎᯒࡣࠊ୍⣽⬊ࡢᰁⰍయᩘࡢኚ໬ࠊ㌿ᗙࡸࡑࡢ௚ࡢ෌ᵓᡂࢆ☜࠿ࡵࡿࡇ࡜ࡀ࡛ࡁࡿࠋࡇࡢᡭἲ࡟ࡼࡾࠊ୍ᐃࡢ⥅௦ᩘཪࡣศ⿣ᩘࡈ࡜࡟ࠊ᰾ᆺࡀ஧ಸయ࡛ಖࡓࢀ࡚࠸ࡿࡇ࡜ࢆ♧ࡍࡢࡣࠊ኱ࡲ࠿࡞㑇ఏⓗᏳᐃᛶࡢᣦᶆ
࡜ࡋ࡚᭷⏝࡛࠶ࡿࠋ࢔ࣞ࢖ CGH ࡣࡼࡾ⊃࠸㑇ఏᏊ㡿ᇦࡢࢥࣆ࣮ᩘኚ໬ࢆ᳨ฟ࡛ࡁࡿ࡜࠸࠺
Ⅼ࡛฼Ⅼࢆ᭷ࡍࡿࠋFISH ࡸḟୡ௦ࢩ࣮ࢡ࢚ࣥࢧ࣮࡟ࡼࡿ᝟ሗ࡟ࡘ࠸࡚ࡣࠊ㑇ఏᏊኚ໬㸦ኚ␗ࡢࢱ࢖ࣉ࡜ࡑࡢ࢔ࣜࣝ㢖ᗘ㸧࡟ᑐࡍࡿ᳨ฟឤᗘ࡜㐺ษ࡞ࢥࣥࢺ࣮ࣟࣝࡢධᡭྍ⬟ᛶࢆㄢ㢟࡜ࡋ᳨࡚ウࡋࡘࡘࠊ㐀⭘⒆ᛶ࡜ࡢ㛵㐃ᛶ࡟ࡘ࠸࡚⛉Ꮫⓗ᳨ドࢆ㐍ࡵࠊヨ㦂ἲ࡜ࡋ࡚฼⏝ࡍࡿࡇ࡜ࡢጇᙜᛶࢆホ౯ࡍ࡭ࡁ࡛࠶ࡿࠋ࡞࠾ࠊᛶ⬟ࡢጇᙜᛶࡀ♧ࡉࢀࡿ࡞ࡽࡤࠊḟୡ௦ࢩ࣮ࢡ
࢚ࣥࢧ࣮࡟ࡼࡿ⡆᫆ᰁⰍయ᳨ᰝ㸦digital karyotyping㸧ࡣࠊ᪥ᩘࡀ࠿࠿ࡾᐃ㔞ᛶ࡟ḞࡅࡿⅬࡀၥ㢟࡜ࡉࢀࡿ G ࣂࣥࢻ᰾ᆺゎᯒࢆ௦᭰ࡍࡿࡇ࡜ࡀ࡛ࡁࡿ࠿ࡶࡋࢀ࡞࠸ࠋ
ᴫࡋ࡚ࠊࡇࢀࡽࡢヨ㦂ࡣ〇ရ⣽⬊ࡢ≉ᛶゎᯒ࡜ࡋ࡚᭷⏝࡛࠶ࡿࡀࠊ⌧᫬Ⅼ࡛ࡣฟⲴᇶ‽࡜࠸࠺ࡼࡾࡶ⣽⬊ࡢ≉ᛶ➼࡟㛵ࡍࡿཧ⪃᝟ሗࢆᚓࡿ࡜࠸࠺┠ⓗ࡛ᐇ᪋ࡉࢀࡿࡶࡢ࡛࠶ࡿࠋ
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㸫㸫㸺ཧ⪃ᩥ⊩㸼
1. World Health Organization. Recommendations for the evaluation of animal cell cultures as substrates for the manufacture of biological medicinal products and for the characterization of cell banks. WHO technical report series, No 978 Annex 3. 2013, http://www.who.
int/biologicals/vaccines/TRS_978_Annex_3.pdf
2. Kuroda T et al. Highly sensitive in vitro methods for detection of residual undifferentiated cells
in retinal pigment epithelial cells derived from human iPS cells. PLoS One. 20127:e37342.
3. Kuroda, T et al. Highly sensitive droplet digital PCR method for detection of residual
undifferentiated cells in cardiomyocytes derived from human pluripotent stem cells. Regen
Therapy –23.
4. Tateno H et al. A medium hyperglycosylated podocalyxin enables noninvasive and quantitative
detection of tumorigenic human pluripotent stem cells. Sci Rep. 
5. Tano K et al. A novel in vitro method for detecting undifferentiated human pluripotent stem cells
as impurities in cell therapy products using a highly efficient culture system. PLoS One.
H
6. Ito M et al. NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model forengraftment of human cells. Blood 2002100:3175-82.
7. Shultz LD et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gammanull mice engrafted with mobilized human hemopoietic stem cells. J Immunol 2005174:6477-89.
8. Kusakawa S et al. Characterization of in vivo tumorigenicity tests using severe immunodeficient
NOD/Shi-scid IL2RȖnull mice for detection of tumorigenic cellular impurities in human cellprocessed therapeutic products. Regen Therapy-7.
9. Machida K et al. Higher susceptibility of NOG mice to xenotransplanted tumors. J Toxicol Sci
200934:123-7.
10. Kanemura H et al. Tumorigenicity studies of induced pluripotent stem cell (iPSC)-derived retinal
pigment epithelium (RPE) for the treatment of age-related macular degeneration. PLoS One.
H
11. Katano I et al. NOD-Rag2null IL-2RȚnull mice: an alternative to NOG mice for generation ofhumanized mice. Exp Anim. 2014;63:321-30.
12. Brehm MA et al. Parameters for establishing humanized mouse models to study human immunity:
analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of micebearing the IL2rgamma(null) mutation. Clin Immunol. -98.
13. Kanemura H et al. Pigment epithelium-derived factor secreted from retinal pigment epithelium
facilitates apoptotic cell death of iPSC. Sci Rep. 20133:2334.
14. Kawamata S et al. Design of a tumorigenicity test for induced pluripotent stem cell (iPSC)-derived
cell products. J Clin Med. -71.

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15. Gropp M et al. Standardization of the teratoma assay for analysis of pluripotency of human ES
cells and biosafety of their differentiated progeny. PLoS ONE. 20127:e45532.
16. Yasuda S et al. Tumorigenicity-associated characteristics of human iPS cell lines. PLoS One.
H
17. Kono K, Takada N et al. Characterization of the cell growth analysis for detection of immortal
cellular impurities in human mesenchymal stem cells. Biologicals. 2015:43:146-9. (See also:
Kono K, Takada N et al. Corrigendum to "Characterization of the cell growth analysis for
detection of immortal cellular impurities in human mesenchymal stem cells" [Biologicals 43 (2)(March 2015) 146-149]. Biologicals. )18. Hasebe-Takada N, Kono K et al. Application of cell growth analysis to the quality assessment of
human cell-processed therapeutic products as a testing method for immortalized cellular
impurities. Regen Ther. 2016;5:49-54. (A corrigendum is in press.)Kusakawa S et al. Ultra-sensitive detection of tumorigenic cellular impurities in human cellprocessed therapeutic products by digital analysis of soft agar colony formation. Sci Rep.

20. Suzuki M et al. Dormant cancer cells retrieved from metastasis-free organs regain tumorigenic
and metastatic potency. Am J Pathol. -81.
21. Shih CC et al. Human embryonic stem cells are prone to generate primitive, undifferentiatedtumors in engrafted human fetal tissues in severe combined immunodeficient mice. Stem Cells
Dev. -902.
22. Fujii E et al. Establishment and characterization of in vivo human tumor models in the
NOD/SCID/ȖCnull mouse. Pathol Int. 2008;58:559-67.
23. Priest CA et al. Preclinical safety of human embryonic stem cell-derived oligodendrocyte
progenitors supporting clinical trials in spinal cord injury. Regen Med. -58.
24. Watanabe S et al. Humanized NOD/SCID/IL2RȖnull mice transplanted with hematopoietic stem
cells under nonmyeloablative conditions show prolonged life spans and allow detailed analysis ofhuman immunodeficiency virus type 1 pathogenesis. J Virol. -64.
25. Nelson DL et al. Alu polymerase chain reaction: a method for rapid isolation of human-specificsequences from complex DNA sources. Proc Natl Acad Sci U S A. -90.
26. Schneider T et al. Quantification of human Alu sequences by real-time PCR--an improved method
to measure therapeutic efficacy of anti-metastatic drugs in human xenotransplants. Clin Exp
0HWDVWDVLV-82.
27. Amariglio N et al. Donor-derived brain tumor following neural stem cell transplantation in an
ataxia telangiectasia patient. PLoS Med 20096: e1000029.
28. Dlouhy BJ et al. Autograft-derived spinal cord mass following olfactory mucosal celltransplantation in a spinal cord injury patient. J Neurosurg. Spine -22.

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29. Berkowitz AL et al. Glioproliferative lesion of the spinal cord as a complication of “Stem-Cell
Tourism”. N Engl J Med. 2016375:196-8.
30. Hertenstein B et al. Development of leukemia in donor cells after allogeneic stem celltransplantation̼a survey of the European Group for Blood and Marrow Transplantation (EBMT).
Haematologica. -75.
31. Garcia S et al. Pitfalls in spontaneous in vitro transformation of human mesenchymal stem cells.
Exp Cell Res. 2010316:1648-50.
32. Torsvik A et al. Spontaneous malignant transformation of human mesenchymal stem cells reflects
cross-contamination: putting the research field on track - letter. Cancer Res. 201070:6393-96.
33. Wang Y et al. Outgrowth of a transformed cell population derived from normal human BM
mesenchymal stem cell culture. Cytotherapy 20057:509-19.
34. Tang DQ et al. In vitro generation of functional insulin-producing cells from human bonemarrow-derived stem cells, but long-term culture running risk of malignant transformation. Am J
Stem Cells 20121:114-27.

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㸫㸫ฟ඾᳨ฟ㝈⏺㸦ୗ⥺㸧᳨ฟ⬟ຊཪࡣ

ḞⅬ࣭␃ពⅬ฼Ⅼ᫬㛫㸦ᩳᏐ㸧

ヨ㦂ᮇ㛫࣭ศᯒ┠ⓗヨ㦂ἲ⮫ᗋ㐺⏝┦ᙜ㒊఩࡬ࡢ⛣᳜࡟ࡼࡾᚤ

ᑓ⏝ື≀᪋タࡀᚲせࢫ࣮ࣝࣉࢵࢺࡀప࠸

⭘⒆ࡢ⏤᮶ࡀᙧ㉁㌿᥮⣽⬊࠿ከ⬟

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Kawamata et al., J Clin Med. 2015

Kanemura et al., Sci Rep. 2013

☜⋡᳨࡛ฟ

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Kuroda et al., PLoS ONE. 2012

Kuroda et al., PLoS ONE. 2012㸦࣐࣮࣮࢝㸸LIN28㸧㸦࣐࣮࣮࢝㸸TRA-1-60㸧࣋ࣝࡣホ౯࡛ࡁ࡞࠸

ಶࠎࡢ⣽⬊࡛ࡢ࣐࣮࣮࢝ศᏊⓎ⌧ࣞ

㛫᥋ⓗ

⡆౽

㧗ឤᗘ

㎿㏿

ࡢ๭ྜ࡛ΰᅾࡍࡿࣄࢺ iPS ⣽⬊ࢆ 50%ࡢ

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hRPE ୰ࡢ 0.002%௨ୗࡢࣄࢺ iPS ⣽⬊ࢤ࣮ࢸ࢕ࣥࢢࡀ⤖ᯝ࡟ᙳ㡪

㛫᥋ⓗ

⡆౽

ࡢⓎ⌧㔞ࢆホ౯ྍ⬟ಶࠎࡢ⣽⬊ࢆゎᯒࡋࠊ࣐࣮࣮࢝ศᏊ▷᫬㛫

⣙ 6 ᫬㛫

ᮍศ໬࡞ከ⬟ᛶᖿ⣽⬊ࡢ᳨ฟqRT-PCRhRPE ୰ࡢ 0.1%ࡢࣄࢺ iPS ⣽⬊

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1᪥

ᮍศ໬࡞ከ⬟ᛶᖿ⣽⬊ࡢ᳨ฟࣇ࣮ࣟࢧ࢖ࢺ࣓ࢺ࣮ࣜ

hRPE2.5 × 105 ಶ୰࡟ 1,000 ಶ㸦0.4%㸧

ホ౯➼ࡀᚲせᛶᖿ⣽⬊࠿ࢆ༊ูࡍࡿ࡟ࡣࠊ⑓⌮ⓗ㈝⏝࡜᫬㛫ࡀ࠿࠿ࡿ

ᑠ⎔ቃ࡛ࡢ㐀⭘⒆ᛶࢆホ౯ྍ⬟┤᥋ⓗ

17~30 㐌㛫㐀⭘⒆ᛶ⣽⬊ࡢ᳨ฟ⓶ୗᢞ୚㸧㸦࣐ࢺࣜࢤࣝ࡜࡜ࡶ࡟ NOG ࣐࢘ࢫ࡟in vivo 㐀⭘⒆ᛶヨ㦂⾲㸯 ΰᅾࡍࡿᮍศ໬ (6L36 ⣽⬊ࡢ᳨ฟ࣭ᐃ㔞ἲ㸫㸫ฟ඾᳨ฟ㝈⏺㸦ୗ⥺㸧᳨ฟ⬟ຊཪࡣ

ḞⅬ࣭␃ពⅬ฼Ⅼ᫬㛫㸦ᩳᏐ㸧

ヨ㦂ᮇ㛫࣭ศᯒ

┠ⓗ

ヨ㦂ἲ

⡆౽

㧗ឤᗘ

㛫᥋ⓗ

ಶࠎࡢ⣽⬊࡛ࡢ࣐࣮࣮࢝ศᏊⓎ⌧

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ࢫ࣮ࣝࣉࢵࢺࡀప࠸

᫬㛫ࡀ࠿࠿ࡿ

ṧᏑ iPS ⣽⬊ࡢ≉ᛶゎᯒࡀྍ⬟

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Kuroda et al., Regen Ther. 2015

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Tateno et al., Sci Rep. 2014⬊
Tano et al., PLoS ONE. 2014ࣄࢺ⬇ⴥయ୰ࡢ 0.1~0.01%ࡢࣄࢺ iPS ⣽㸦࣐࣮࣮࢝㸸H3+࣏ࢻ࢝ࣜ࢟ࢩࣥ㸧

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㸦࣐࣮࣮࢝㸸LIN28㸧

ᇵᆅᡂศࡀ⤖ᯝ࡟ᙳ㡪ࣞ࣋ࣝࡣホ౯࡛ࡁ࡞࠸

ಶࠎࡢ⣽⬊࡛ࡢ࣐࣮࣮࢝ศᏊⓎ⌧㛫᥋ⓗ㧗ࢫ࣮ࣝࣉࢵࢺ

⡆౽⣽⬊㠀◚ቯⓗ⣙ 1 㐌㛫

ᮍศ໬࡞ከ⬟ᛶᖿ⣽⬊ࡢ᳨ฟ

Essential-8/LN521 ᇵ㣴ቑᖜἲHEK293T ⣽⬊୰ࡢ 0.05%ࡢࣄࢺ iPS ⣽⬊ hMSC ୰ࡢ 0.01~0.001%ࡢࣄࢺ iPS ⣽⬊

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㸦ᇵ㣴ୖΎᅇ཰࠿ࡽ ᐃࡲ࡛㸧

3 ᫬㛫௨ୗ

ᮍศ໬࡞ከ⬟ᛶᖿ⣽⬊ࡢ᳨ฟGlycoStem-HP ἲࣄࢺᚰ➽⣽⬊୰ࡢ 0.001%ࡢࣄࢺ iPS ⣽⬊ࣞ࣋ࣝࡣホ౯࡛ࡁ࡞࠸

㎿㏿

⣙ 6 ᫬㛫

ᮍศ໬࡞ከ⬟ᛶᖿ⣽⬊ࡢ᳨ฟ

Droplet Digital PCR⾲㸯㸦⥆㸧 ΰᅾࡍࡿᮍศ໬ (6L36 ⣽⬊ࡢ᳨ฟ࣭ᐃ㔞ἲ㸫㸫 ᝏᛶᙧ㉁㌿᥮⣽⬊ࢆ༢㞳࣭≉ᛶゎᯒ࡛ࡁࡿ 㧗ឤᗘ ⮫ᗋ㐺⏝┦ᙜ㒊఩࡬ࡢ⛣᳜ ࢖࣓࣮ࢪࢫ࢟ࣕࢼ࣮ࡀ㧗౯ ᝏᛶᙧ㉁㌿᥮⣽⬊௨እࡢ୙ ᾋ㐟⣔⣽⬊࡟ࡣ౑࠼࡞࠸ ᝏᛶᙧ㉁㌿᥮⣽⬊௨እࡢ୙Ṛ໬⣽⬊ࡣ᳨ฟ୙⬟ ⭘⒆ࡢ⏤᮶ࡀᙧ㉁㌿᥮⣽⬊࠿ከ⬟ᛶᖿ⣽⬊࠿ࢆ༊ูࡍ

ࡿ࡟ࡣࠊ⑓⌮ⓗホ౯➼ࡀᚲせ୙Ṛ໬⣽⬊ࡣ᳨ฟ୙⬟ in vivo 㐀⭘⒆ᛶࢆ♧ࡉ࡞࠸ ᾋ㐟⣔⣽⬊࡟ࡣ౑࠼࡞࠸ⓗ࡟ุ᩿ ᑓ⏝ື≀᪋タࡀᚲせṚ໬⣽⬊ࡣ᳨ฟ୙⬟ⓗ࡟ุ᩿ 㐀⭘⒆ᛶ⣽⬊ࡢ᭷↓ࡣ㛫᥋ 㐀⭘⒆ᛶ⣽⬊ࡢ᭷↓ࡣ㛫᥋ᛶゎᯒ࡛ࡁࡿ ᝏᛶᙧ㉁㌿᥮⣽⬊ࢆ༢㞳࣭≉ 㧗ឤᗘ

 ㈝⏝࡜᫬㛫ࡀ࠿࠿ࡿᛶࢆホ౯ྍ⬟

࡟ࡼࡾᚤᑠ⎔ቃ࡛ࡢ㐀⭘⒆ Ᏻ౯

3~4 㐌㛫

㸦ᝏᛶᙧ㉁㌿᥮⣽⬊㸧ࡢ᳨ฟ㸦ᝏᛶᙧ㉁㌿᥮⣽⬊㸧ࡢ᳨ฟ
3~4 㐌㛫

㊊ሙ㠀౫ᏑⓗቑṪ㌾ᐮኳࢥࣟࢽ࣮ᙧᡂヨ㦂ࢹࢪࢱࣝ㊊ሙ㠀౫ᏑⓗቑṪ㌾ᐮኳࢥࣟࢽ࣮ᙧᡂヨ㦂 ┤᥋ⓗ16 㐌㛫௨ୖ㐀⭘⒆ᛶ⣽⬊ࡢ᳨ฟ࢘ࢫ࡟⓶ୗᢞ୚㸧㸦࣐ࢺࣜࢤࣝ࡜࡜ࡶ࡟ NOG ࣐༊ู࡛ࡁ࡞࠸ ᝏᛶᙧ㉁㌿᥮⣽⬊ࡢ᭷↓ࢆⓗ࡟ุ᩿ 㐀⭘⒆ᛶ⣽⬊ࡢ᭷↓ࡣ㛫᥋Ṛ໬⣽⬊ࡶᖜᗈࡃ᳨ฟ ᝏᛶᙧ㉁㌿᥮⣽⬊௨እࡢ୙

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4 㐌㛫௨ୖ

㸦ᙧ㉁㌿᥮⣽⬊㸧ࡢ᳨ฟ୙Ṛ໬⣽⬊⣽⬊ቑṪ≉ᛶゎᯒ

ฟ඾

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Kusakawa et al., Regen Ther. 2015 Kusakawa et al., Regen Ther. 2015ฟ㝈⏺ࡣ 0.02㸣㸧
Kusakawa et al., Sci Rep. 2015࡛ΰᅾࡍࡿ HeLa ⣽⬊㸦10 ಶ㸧ࢆ ΰᅾࡍࡿ HeLa ⣽⬊㸦ィ⟬ୖࡢ᳨ ྜ࡛ΰᅾࡍࡿ HeLa ⣽⬊᳨ฟ㝈⏺ 17%ࡢ☜⋡᳨࡛ฟྍ⬟ཪࡣHasebe-Takada et al., Regen Ther. 2016

Kono et al., Biologicals. 2015&2017࡛ΰᅾࡍࡿ୙Ṛ໬⬡⫫⏤᮶ᖿ⣽⬊᮶ᖿ⣽⬊࡟ 1/105㸦0.001㸣㸧ࡢ๭ྜ࡛ΰᅾࡍࡿ HeLa ⣽⬊ཬࡧ⬡⫫⏤᳨ฟ⬟ຊ hMSC ࡟ 1/106㸦0.0001㸣㸧ࡢ๭ྜ hMSC ࡟ 1/103㸦0.1㸣㸧ࡢ๭ྜ࡛ hMSC ࡟ 1/107㸦0.00001㸣㸧ࡢ๭ hMSC ࡟ 1/106㸦0.0001㸣㸧ࡢ๭ྜ

␃ពⅬ

ḞⅬ࣭

฼Ⅼ

ヨ㦂ᮇ㛫

┠ⓗ

ヨ㦂ἲ

in vivo 㐀⭘⒆ᛶヨ㦂⾲㸰 ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊ࡢ᳨ฟ࣭ᐃ㔞ἲ㸺ཧ⪃᝟ሗ 㸼ΰᅾࡍࡿᮍศ໬ (6L36 ⣽⬊ࡢ᳨ฟἲ࡜ࡋ࡚ࡢ LQYLYR 㐀⭘⒆ᛶヨ㦂ฟ඾㸸Kanemura et al. Tumorigenicity studies of induced pluripotent stem cell (iPSC)-derived retinal
pigment epithelium (RPE) for the treatment of age-related macular degeneration.
PLoS ONE. 2014;9:e85336.

࠙᪉ἲࠚ
1. ⣽⬊ᇵ㣴 ⓶⭵⥺⥔ⱆ⣽⬊࡟ࣞࢺࣟ࢘࢖ࣝࢫpMXs-POU5F1ࠊ-Sox2ࠊ-c-Mycࠊ-Klf4ࢆᑟධࡋ࡚స〇ࡉࢀࡓࣄࢺiPS⣽⬊ᰴ201B7ࡣࠊSNLࣇ࢕࣮ࢲ࣮⣽⬊ୖ࡛5 ng/mL bFGFࢆྵࡴReproFF2ᇵᆅࢆ
⏝࠸࡚⥔ᣢᇵ㣴ࡍࡿࠋ⣽⬊ᰴ836B1ࡣ೺ᖖே࠿ࡽ᥇ྲྀࡋࡓ⓶⭵⥺⥔ⱆ⣽⬊࠿ࡽᶞ❧ࡉࢀࡓࠋ⣽⬊ᰴ59ࠊK11ࠊ K21ࠊ 101ࠊRNT9ཪࡣRNT10ࡣࠊྠពࢆᚓࡓ6ྡࡢගཷᐜయ≉␗ⓗ㑇ఏᏊኚ␗ࢆక࠺⥙⭷Ⰽ⣲ኚᛶ⑕ᝈ⪅ࡢ⓶⭵⥺⥔ⱆ⣽⬊࡟⏤᮶ࡍࡿࠋ⓶⭵⥺⥔ⱆ⣽⬊࠿ࡽࠊ
POU5F1ࠊSOX2ࠊKLF4ࠊMYCLࠊLIN28AཬࡧGLIS1㸦iPS⣽⬊ᰴ59-GࠊK21-Gࠊ101-GࠊRNT9ࠊ
RNT10㸧ཪࡣPOU5F1ࠊSOX2ࠊKLF4ࠊMYCLࠊLIN28Aཬࡧp53shRNA㸦iPS⣽⬊ᰴ101-EVࠊ
K11-EVࠊK21-EV㸧ࡀᤄධࡉࢀࡓENBA࢚ࣆࢯ࣮࣐ࣝ࣋ࢡࢱ࣮࡟ࡼࡾࠊiPS⣽⬊ࢆᶞ❧ࡋࡓࠋ
ࡇࢀࡽࡢiPS⣽⬊ࡣࠊ⮬ᕫ⥺⥔ⱆ⣽⬊⏤᮶ࣇ࢕࣮ࢲ࣮⣽⬊ୖ࡛ࠊ5 ng/mL bFGFࢆྵࡴprimateESᇵᆅࢆ⏝࠸࡚⥔ᣢᇵ㣴ࡍࡿࠋiPS⣽⬊⏤᮶⥙⭷Ⰽ⣲ୖ⓶㸦RPE㸧⣽⬊ࢡ࣮ࣟࣥ㸦59-G3 RPEࠊK21-G18 RPEࠊ101-G25 RPEࠊRNT9 RPEࠊRNT10 RPEࠊ101-EV RPEࠊK11-EV9 RPEཪࡣK21EV15 RPE㸧ࡣࠊRPE⥔ᣢᇵᆅ㹙B-27ࢧࣉ࣓ࣜࣥࢺࠊ2 mM L-ࢢࣝࢱ࣑ࣥࠊ 0.5 nM SB431542
ཬࡧ10 ng/mL bFGFࢆྵࡴDulbecco’s Modified Eagle’s Medium: Ham's F12 Medium㸦7: 3㸧㹛࡛⥔ᣢᇵ㣴ࡍࡿࠋࣄࢺึ௦ᇵ㣴RPEࡣࠊL-ࢢࣝࢱ࣑ࣥࠊGA-1000ཬࡧbFGFࢆྵࡴRetinal Pigment
Epithelial Cell Basal Medium࡛⥔ᣢᇵ㣴ࡍࡿࠋᾋ㐟ᇵ㣴ࡋࡓࣄࢺiPS⣽⬊⏤᮶RPE⣽⬊ࡣࠊ⓶ୗᢞ୚ཪࡣࢥ࣮ࣛࢤࣥࢤࣝୖ࡟ᤥ࠸࡚ࢥ࣮ࣛࢤ࡛ࣥᯫᶫࡉࡏࡓRPE⣽⬊ࢩ࣮ࢺస〇࡟⏝࠸
ࡿࠋRPE⣽⬊ࢩ࣮ࢺࡣࠊ10%࢘ࢩ⫾ඣ⾑Ύ㸦FBS㸧࡜Ham's F10ᇵᆅ࡛4㐌㛫ࠊRPE⥔ᣢᇵᆅ࡛
3㐌㛫⥔ᣢᇵ㣴ࡋࡓᚋ࡟ࠊࢥࣛࢤࢼ࣮ࢮI࡛ࢥ࣮ࣛࢤࣥࢤࣝ࠿ࡽ๤㞳ࡉࡏࡿࠋRPE⣽⬊ࢩ࣮ࢺࡣࠊᠱ⃮⣽⬊࡜࣐ࢺࣜࢤࣝࢆΰྜࡋ⓶ୗᢞ୚ཪࡣ࣮ࣞࢨ࣮࣐࢖ࢡࣟࢲ࢖ࢭࢡࢩࣙࣥ࡟ࡼࡾ
᩿∦໬ࡋື≀ࡢ⥙⭷⛣᳜࡟⏝࠸ࡿࠋ

2. ື≀ᐇ㦂
2.1 ࣐࢘ࢫ⓶ୗ⛣᳜ ᵝࠎ࡞ᢞ୚㔞ࡢHeLa⣽⬊ࢆࠊ200 Lࡢ࣐ࢺࣜࢤࣝ࡜ΰྜཪࡣ200 LࡢPBS㸦࣐ࢺࣜࢤࣝ࡞
ࡋ㸧࡟ᠱ⃮ࡋࠊ7ࠥ8㐌㱋ࡢ㞤ᛶࢾ࣮ࢻ࣐࢘ࢫ㸦BALB/cAJCl-nu/nu㸧ࠊSCID࣐࢘ࢫ㸦C.B-17/Icrscid/scidJcl㸧ࠊNOD-SCID࣐࢘ࢫ㸦NOD/ShiJic-scidJcl㸧ཪࡣNOG࣐࢘ࢫ㸦NOD/ShiJic-scidࠊ㸫㸫



IL-2RȖKO Jic㸧ࡢ⓶ୗ⤌⧊࡟ࠊ26Gὀᑕ㔪ࢆ௜ࡅࡓ1 mLࢩࣜࣥࢪࢆ⏝࠸࡚ὀᑕࡍࡿࠋື≀ࡣ36㐌㛫ࣔࢽࢱ࣮ࡍࡿࠋᐇ㦂ࡢ⤊ࢃࡾ࡟࣐࢘ࢫࢆᏳᴦṚࡉࡏࠊ⭘⒆ࢆ᥇ྲྀࡋࠊ4%ࣃ࣒ࣛ࣍ࣝ
࢔ࣝࢹࣄࢻ࡛ᅛᐃࡍࡿࠋࣃࣛࣇ࢕ࣥษ∦ࡣࠊ⑓⌮Ꮫⓗ࡞ほᐹࡢࡓࡵHEᰁⰍࡍࡿࠋᵝࠎ࡞ᢞ୚㔞ࡢࣄࢺiPS⣽⬊201B7ཪࡣ1 x 106ಶࡢࣄࢺiPS⣽⬊⏤᮶RPE⣽⬊ࢆࠊ200 Lࡢ࣐ࢺࣜࢤࣝ
࡜ΰྜཪࡣ200 LࡢPBS㸦࣐ࢺࣜࢤࣝ࡞ࡋ㸧࡟ᠱ⃮ࡋࠊ7ࠥ8㐌㱋ࡢ㞤ᛶNOG࣐࢘ࢫ࡟ࠊ26G
ὀᑕ㔪ࢆ௜ࡅࡓ1 mLࢩࣜࣥࢪࢆ⏝࠸࡚⓶ୗᢞ୚ࡋࠊ6ࠥ15ࣨ᭶ほᐹࡍࡿࠋᐇ㦂ࡢ⤊ࢃࡾ࡟࣐࢘ࢫࢆᏳᴦṚࡉࡏࠊ⛣᳜∦ࢆࣆࣥࢭࢵࢺ࡛᥇ྲྀࡋࠊ4%ࣃ࣒ࣛ࣍ࣝ࢔ࣝࢹࣄࢻ࡛ᅛᐃࡍࡿࠋ

2.2 ࣛࢵࢺ⥙⭷ୗᢞ୚ 3㐌㱋㞤ᛶࢾ࣮ࢻࣛࢵࢺ㸦F344/NJcl-rnu/rnu㸧ࢆࠊࢣࢱ࣑ࣥ100 mg/kg࡜࢟ࢩࣛࢪࣥ10 mg/kg
࡜ࡢΰᾮࡢ⭡⭍ෆᢞ୚࡟ࡼࡾ㯞㓉ࡍࡿࠋᩓ▖⸆㸦0.5%ࢺࣟࣆ࣑࢝ࢻࠊ0.5%ࣇ࢙ࢽࣞࣇࣜࣥሷ
㓟ሷ㸧࡟ࡼࡾྑ║ࡢ▖Ꮝࢆᣑ኱ࡍࡿࠋ27Gὀᑕ㔪ࢆ⏝࠸࡚ྑ║㝮ࡢᙉ⭷ࢆᑠࡉࡃษ㛤ࡍࡿࠋࡑࡢᚋࠊᵝࠎ࡞⃰ᗘࡢHeLa⣽⬊ࠊࣄࢺiPS⣽⬊ཪࡣ2 LࡢDMEM/F12ᇵᆅ࡟ᾐࡋࡓ1 mmᅄ᪉ࡢࣄࢺiPS⣽⬊⏤᮶RPE⣽⬊ࢩ࣮ࢺࢆࠊ33Gὀᑕ㔪ࡢ௜࠸ࡓࣁ࣑ࣝࢺࣥࢩࣜࣥࢪࢆ⏝࠸࡚ࠊᙉ⭷ษ㛤㒊࠿ࡽ⥙⭷ୗࢫ࣮࣌ࢫ࡟ὀᑕࡍࡿࠋ⣽⬊ཪࡣRPE⣽⬊ࢩ࣮ࢺࡣࠊእ⛉⏝㢧ᚤ㙾ୗ࡛ᣑ኱ࡋࡓ▖Ꮝࢆ㏻ࡋ࡚ࣁ࣑ࣝࢺࣥࢩࣜࣥࢪࡢ఩⨨ࢆ☜ㄆࡋ࡞ࡀࡽࠊ⥙⭷ୗࡢẟ⣽⾑⟶㞟⥙࡟⛣᳜ࡍࡿࠋ⥙⭷ୗࡢẟ⣽⾑⟶㞟⥙ࡣࠊ࢔ࣝࣅࣀࡢࢾ࣮ࢻࣛࢵࢺ࡟࠾࠸࡚ᐜ᫆࡟ほᐹ࡛ࡁࠊ⥙⭷ୗࢫ࣮࣌ࢫࡢ┠༳࡜ࡋ࡚౑࠺ࠋ⛣᳜ࡋࡓࢾ࣮ࢻࣛࢵࢺࡣ8ࠥ82㐌㛫ࣔࢽࢱ࣮ࡍࡿࠋᐇ㦂ࡢ⤊ࢃࡾ࡟ࣛࢵࢺࡣᏳᴦṚࡉࡏࠊ⛣᳜ࡋࡓ඲║⌫ࢆ᥇ྲྀࡋࠊ4%ࣃ࣒ࣛ࣍ࣝ࢔ࣝࢹࣄࢻ࡛ᅛᐃ
ࡍࡿࠋ

3. RT-PCRཬࡧᐃ㔞RT-PCR ⥲RNAࡣ࢟ࢵࢺ࡟ࡼࡾᢳฟࡋࠊΰᅾࡍࡿࢤࣀ࣒DNAࡣࢫࣆ࣒ࣥ࢝ࣛฎ⌮࡟ࡼࡾ㝖ཤࡍࡿࠋ
PrimeScript RT Master Mix࡜PrimeSTAR MAX DNA Polymeraseࢆ⏝࠸࡚ࠊ50 ngࡢ⥲RNA࠿ࡽ
cDNAࢆస〇ࡍࡿࠋᐃ㔞PCRࡣSYBR Greenࢆ⏝࠸࡚⾜࠸ࠊ㑇ఏᏊⓎ⌧㔞ࡣGAPDH࡛⿵ṇࡍࡿࠋᐃ㔞RT-PCRࡣQuantiTect Probe RT-PCR Kitࢆ⏝࠸࡚⾜࠺ࠋᶆⓗ㑇ఏᏊࡢⓎ⌧㔞ࡣࠊRNase
P㌿෗⏘≀࡟ࡼࡾ⿵ṇࡍࡿࠋᐃ㔞RT-PCRࡣࠊ45ࢧ࢖ࢡࣝ⾜࠺ࠋᮏᐇ㦂࡛⏝࠸ࡿࣉ࣮ࣟࣈ࡜ࣉ
ࣛ࢖࣐࣮ࡢ㓄ิࡣࠊ⾲.ࣉ࣮ࣟࣈ࡜ࣉࣛ࢖࣐࣮ࡢ㓄ิ㸦ཧ⪃᝟ሗ㸯㸧࡟グ㍕ࡍࡿࠋ

4. Alu PCR ࣄࢺ⣽⬊≉␗ⓗ࡞Alu㓄ิࢆࣉࣛ࢖࣐࣮ࡢࢹࢨ࢖ࣥ࡟⏝࠸ࡿࠋPCR཯ᛂ㸦28ࢧ࢖ࢡࣝ㸧࡟ࠊAluࣉࣛ࢖࣐࣮5-AAGTCGCGGCCGCTTGCAGTGAGCCGAGAT-3ࠊ50 ng DNAࢸࣥࣉ࣮ࣞ
ࢺཬࡧPrimeSTAR Max DNA Polymeraseࢆ⏝࠸ࡿࠋࣄࢺHeLa⣽⬊ DNA㸸࣐࢘ࢫNIH3T3 DNA㸫㸫ࡀᵝࠎ࡞๭ྜࡢDNAࢸࣥࣉ࣮ࣞࢺࢆࠊAlu PCRࡢ᳨ฟឤᗘࢆỴᐃࡍࡿࡓࡵ࡟⏝࠸ࡿࠋPCR⏘≀ࡣ1%࢔࣮࢞ࣟࢫࢤࣝࢆ⏝࠸ࡓ㟁ẼὋື࡛ศ㞳ࡋࠊࡑࡢ⏬ീࡣࢹࢪࢱࣝ໬ࡋ࡚ྲྀࡾ㎸ࡴࠋ

5. ච␿⤌⧊໬Ꮫ ⛣᳜ࡋࡓ⤌⧊ࡣ 4%ࣃ࣒ࣛ࣍ࣝ࢔ࣝࢹࣄࢻ࡛ᅛᐃࡍࡿࠋࣃࣛࣇ࢕ࣥໟᇙࡋࡓ⤌⧊ษ∦ࡣࠊHE ᰁⰍࡍࡿࠋࡑࡢᚋࠊࣃࣛࣇ࢕ࣥษ∦ࡣ⬺ࣃࣛࣇ࢕ࣥ໬ࡢࡓࡵࠊ࢟ࢩ࡛ࣞࣥฎ⌮ࡋࠊ100%ࠊ
95%ࠊ80%ࠊ70%࢚ࢱࣀ࣮࡛ࣝྛࠎ5 ศ㛫ࡎࡘ㐃⥆ࡋ࡚ฎ⌮ࢆ⾜࠺ࠋษ∦ࡣ 10 mM ࢡ࢚ࣥ㓟
㸦pH 6㸧࡛ Û&ࠊ50 ศ㛫ฎ⌮ࡋࠊ0.4%Triton-X100/PBS ࡛ᐊ ࠊ30 ศ㛫ฎ⌮ࡍࡿࠋ⬺ࣃࣛࣇ࢕ࣥ໬ษ∦ࡣࠊᢠࣄࢺ Lamin-A ᢠయࠊᢠ BEST1 ᢠయཬࡧᢠ Ki-67 ᢠయ࡛ᰁⰍࡍࡿࠋ᰾ࡣࠊ
Hoechst 33258 ཪࡣ DAPI ࡛ᰁⰍࡍࡿࠋᾋ㐟≧ែࡢࣄࢺ iPS ⣽⬊⏤᮶ RPE ⣽⬊ࡣࠊ4%ࣃࣛ࣍
࣒ࣝ࢔ࣝࢹࣄࢻ࡛ᅛᐃࡋࠊᢠ POU5F1㸦OCT3/4㸧ᢠయཪࡣᢠ BEST1 ᢠయ࡛ᰁⰍࡍࡿࠋᢠయ
ࡣࠊAlexa Fluor 488 goat anti-mouse ཪࡣ Alexa Flour 488 goat anti-rabbit ࢆ⏝࠸࡚ྍど໬ࡍࡿࠋ⺯ග㢧ᚤ⏬ീࡣࠊ⺯ග㢧ᚤ㙾࡟ࡼࡾྲྀࡾ㎸ࡴࠋ㸫㸫㸫㸫Forward primer sequence (5'Ѝ3')
CACGGTGCGGGCATCTGGAAACCCACACTGCAGCAGA
ATCAGAGGCCAGGCTACTACAGGACTGGGGTTAAATCTCACAGC
TTAACACACTTGAGCCATCACC
AGCCCAGCATCATTCTTCTCCGATGCTGGCGCTGAGTAC

Probe sequence (5'Ѝ3')
CGCATGGGGTTCGGCTTCCTGTCCCGGACCACATCCTTCTCGAGCCCAAGC

Primers for RT-PCR

Gene

LIN28A

POU5F1BEST1CRALBP

PAX6

TYR

GAPDH

Probes and primers for qRT-PCR

Gene

LIN28A

POU5F1⾲ࣉ࣮ࣟࣈ࡜ࣉࣛ࢖࣐࣮ࡢ㓄ิ㸦ཧ⪃᝟ሗ 1㸧

GAAACCCACACTGCAGCAGACACGGTGCGGGCATCTG

Forward primer sequence (5'Ѝ3')



CCACCACTGACACGTTGGC

GGCGTTCCATTGCATAAAGAAAATCTCGGATGTCTGTCCACTTGACATGTTGCCTATGGAAGAC

TCCACAGTTTTCCTCCTCACTT

TCGCTTGCCCTTCTGGCG

CCTTCCATGTGCAGCTTACTC

Reverse primer sequence (5'Ѝ3')



TCGCTTGCCCTTCTGGCG

CCTTCCATGTGCAGCTTACTC

Reverse primer sequence (5'Ѝ3')

























㸺ཧ⪃᝟ሗ 㸼ΰᅾࡍࡿᮍศ໬ (6L36 ⣽⬊ࡢ᳨ฟἲ࡜ࡋ࡚ࡢ T573&5
ฟ඾㸸Kuroda et al. Highly sensitive in vitro methods for detection of residual undifferentiated cells
in retinal pigment epithelial cells derived from human iPS cells.
PLoS ONE. 2012;7(5):e37342
࠙᪉ἲࠚ
1. Total RNA ᢳฟ࢟ࢵࢺ࡟ῧ௜ࡉࢀ࡚࠸ࡿࣉࣟࢺࢥ࣮ࣝ࡟ᚑࡗ࡚ࠊࢧࣥࣉࣝ࡜࡞ࡿ⣽⬊㸦iPS ⣽⬊ࢆศ໬ࡉࡏࡓ⣽⬊࡞࡝㸧࠿ࡽ⥲ RNA ࢆᢳฟࡋࠊDNase ฎ⌮ࢆ⾜࠺ࠋ
2. ᐃ㔞 RT-PCR
2.1 PCR mixture ࢆ QuantiTect Probe RT-PCR Kit ࢆ⏝࠸࡚௨ୗࡢࡼ࠺࡟ㄪ〇ࡍࡿࠋa)

PCR mixture㸦LIN28㸧
Final conc.

Assay/well (L)

QuantiTect RT Mix

1×

0.25

2 × QuantiTect Probe RT-PCR Master Mix

1×

12.5

100 M Forward Primer

0.4 M

0.1

100 M Reverse Primer

0.4 M

0.1

20 M Probe

0.1 M

0.125

RNAase free water-

6.93
Total 20b)PCR mixture㸦GAPDH㸧
Final conc.

Assay/well (L)

QuantiTect RT Mix

1×

0.25

2 × QuantiTect Probe RT-PCR Master Mix

1×

12.5

10 M Forward Primer

0.2 M

0.5

10 M Reverse Primer

0.2 M

0.5

5 M Probe

0.1 M

0.5

RNAase free water-

5.75
Total 20

TaqMan® GAPDH Control Reagents (human)ࢆ౑⏝2.2 Total RNA ⁐ᾮࢆ௨ୗࡢࡼ࠺࡟ㄪ〇ࡍࡿࠋ
a)

LIN28

ᐃ⏝

࣭ ᳨㔞⥺⏝ࡢࢸࣥࣉ࣮ࣞࢺࡢㄪ〇ᮍศ໬ iPS ⣽⬊⏤᮶ RNA ⃰ᗘࢆ 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001, 0 ng/L ࡜࡞㸫㸫ࡿࡼ࠺࡟ RNase free water ࡛ᕼ㔘ࡋࡓࡶࡢࢆㄪ〇ࡍࡿࠋ࣭ ࢧࣥࣉࣝ RNA ࡢㄪ〇ࢧࣥࣉࣝ RNA ࡢ⃰ᗘࡀ 10 ng/L ࡟࡞ࡿࡼ࠺࡟ㄪ〇ࡍࡿࠋ
 
b)

GAPDH

ᐃ⏝

࣭ ᳨㔞⥺⏝ࡢࢸࣥࣉ࣮ࣞࢺࡢㄪ〇ᮍศ໬ iPS ⣽⬊⏤᮶ RNA ⃰ᗘࢆ 10, 3, 1, 0.3, 0.01, 0 ng/L ࡜࡞ࡿࡼ࠺࡟ RNase
free water ࡛ᕼ㔘ࡋࡓࡶࡢࢆㄪ〇ࡍࡿࠋ࣭ ࢧࣥࣉࣝ RNA ࡢㄪ〇ࢧࣥࣉࣝ RNA ࡢ⃰ᗘࡀ 1 ng/L ࡟࡞ࡿࡼ࠺࡟ RNase free water ࡛ᕼ㔘ࡋࡓࡶࡢࢆ
ㄪ〇ࡍࡿࠋ
2.3 PCR ⏝ 96 ࢙࢘ࣝࣉ࣮ࣞࢺ࡟ PCR mixture ࢆ 20 L/࢙࢘ࣝࡎࡘῧຍࡍࡿࠋ
2.4 ࢸࣥࣉ࣮ࣞࢺ⁐ᾮࢆ 5 L/࢙࢘ࣝࡎࡘῧຍࡍࡿ㸦ࡼࡃΰྜࡍࡿ㸧ࠋ
2.5 ࣜ࢔ࣝࢱ࢖࣒ PCR ⿦⨨࡟ࢭࢵࢺࡍࡿࠋ
ᐃ㔞 RT-PCR ᮲௳
Stage

ᗘ

᫬㛫

Stage 1

50.0Υ

30 ศ

Stage 2

95.0Υ

15 ศ

94.0Υ

15 ⛊

60.0Υ

1ศ

Stage 3

Stage 3 ࢆ 45 ࢧ࢖ࢡࣝ⧞ࡾ㏉ࡍ㸬㸦GAPDH ࡣ 40 ࢧ࢖ࢡࣝ㸧㸫㸫㸦ࢧࣥࣉࣝ AࠊBࠊC ࡜ࡍࡿ㸧ࣉ࣮ࣞࢺ㓄⨨ᅗ
GAPDH

LIN28

1

2

3

A

201B7

201B7

201B7

B

A

A

A

A

A

A

C

B

B

B

B

B

B

D

C

C

C

C

C

C

E

S10

S3

S1

S3

S1

S0.3

F

S0.3

S0.1

DW

S0.1

S0.03

S0.01

S0.003 S0.001

DW



G
H

4

5

6

7

8









9

10

11

12

201B7* 201B7* 201B7*

*ᮍศ໬࣐࣮࣮࢝ࢆ ᐃࡍࡿ 201B7 ࡣ 1 ng/L ࡛ㄪ〇ࡍࡿ㸦㝧ᛶᑐ↷㸧ࠋ
LIN28 probeࠊprimer 㓄ิ
Gene

LIN28

Probe Primer set 㸦5´ Ѝ 3´)
Probe sequences㸦5´ FAM/3´ TAMRA㸧CGCATGGGGTTCGGCTTCCTGTCC

Forward primer sequences

CACGGTGCGGGCATCTG

Reverse primer sequences

CCTTCCATGTGCAGCTTACTC

Primer ࡣ 100 MࠊProbe ࡣ 20 M ࡟ㄪ〇ࡍࡿࠋὀពⅬࡈࡃᚤ㔞࡞ LIN28 ࢆ᳨ฟࡋࡓሙྜࡢุ᩿ᇶ‽࡜ࡋ࡚ࠊCt ್ࡀ 35 ࢆ㉸࠼ࡓሙྜࡣᮍ
᳨ฟ࡜ࡍࡿࠋ
㸦Ct ್>35 ࡛ࡣࣂࣛࢶ࢟ࡀ኱ࡁࡃ࡞ࡿࡓࡵ㸧㸫㸫㸺ཧ⪃᝟ሗ 㸼ΰᅾࡍࡿᮍศ໬ (6L36 ⣽⬊ࡢ᳨ฟἲ࡜ࡋ࡚ࡢ 'URSOHW'LJLWDO3&5ฟ ඾ 㸸 Kuroda et al. Highly sensitive droplet digital PCR method for detection of residual
undifferentiated cells in cardiomyocytes derived from human pluripotent stem cells.
Rege Ther. 2015;2:17-23.
࠙᪉ἲࠚ
1. Total RNA ᢳฟ࢟ࢵࢺ࡟ῧ௜ࡉࢀ࡚࠸ࡿࣉࣟࢺࢥ࣮ࣝ࡟ᚑࡗ࡚ࠊࢧࣥࣉࣝ࡜࡞ࡿ⣽⬊㸦iPS ⣽⬊ࢆศ໬ࡉࡏࡓ⣽⬊࡞࡝㸧࠿ࡽ⥲ RNA ࢆᢳฟࡋࠊDNase ฎ⌮ࢆ⾜࠺ࠋ
2. Droplet digital PCR
2.1 PCR mixture ࢆ One-Step RT-ddPCR Kit for Probes ࢆ⏝࠸࡚௨ୗࡢࡼ࠺࡟ㄪ〇ࡍࡿࠋ
PCR mixture
Final conc.

Assay/well (L)

1×

10

25 mM Manganese

1×

0.8

50 M Forward Primer

0.75 M

0.3

50 M Reverse Primer

0.75 M

0.3

50 M Probe

0.25 M

0.1

RNAase free water-

3.5

2 × One-Step RT-ddPCR Supermix

Total 15

2.2 Total RNA ⁐ᾮࢆ௨ୗࡢࡼ࠺࡟ㄪ〇ࡍࡿࠋ
LIN28

ᐃ⏝

࣭ ᳨㔞⥺⏝ࡢࢸࣥࣉ࣮ࣞࢺࡢㄪ〇ᮍศ໬ iPS ⣽⬊⏤᮶ RNA ⃰ᗘࢆ 0.1, 0.03, 0.01, 0.003, 0.001, 0 ng/L ࡜࡞ࡿࡼ࠺
࡟ RNase free water ࡛ᕼ㔘ࡋࡓࡶࡢࢆㄪ〇ࡍࡿࠋ࣭ ࢧࣥࣉࣝ RNA ࡢㄪ〇ࢧࣥࣉࣝ RNA ࡢ⃰ᗘࡀ 10 ng/L ࡟࡞ࡿࡼ࠺࡟ㄪ〇ࡍࡿࠋ
2.3 PCR tube ࡟ PCR mixture ࢆ 15 L/࢙࢘ࣝࡎࡘῧຍࡍࡿࠋ
2.4 RNA ⁐ᾮࢆ 5 L/࢙࢘ࣝࡎࡘῧຍࡍࡿࠋ
㸦ࡼࡃΰྜࡍࡿ㸧
2.5 Droplet Generator ࢆ⏝࠸࡚ࠊࢻࣟࢵࣉࣞࢵࢺస〇ࢆ⾜࠺ࠋ
2.6 సᡂࡋࡓࢻࣟࢵࣉࣞࢵࢺᾮࢆ 96 ࢙࢘ࣝࣉ࣮ࣞࢺ࡟⛣ࡍࠋ
2.7 RT-PCR ཯ᛂࢧ࣮࣐ࣝࢧ࢖ࢡ࣮ࣛ᮲௳

㸫㸫



Stage

ᗘ

᫬㛫

Stage 1

60.0Υ

30 ศ

Stage 2

95.0Υ

5ศ

94.0Υ

30 ⛊

64.0Υ

1ศ

Stage 3

Stage 3 ࢆ 40 ࢧ࢖ࢡࣝ⧞ࡾ㏉ࡍࠋ
Stage 498Υ

10 ศ

2.8 PCR ཯ᛂᾮࢆ QX100 Droplet Reader ࢆ⏝࠸࡚ゎᯒࡍࡿࠋ
LIN28 probeࠊ primer 㓄ิ
Gene

LIN28

Sequence㸦5´ Ѝ 3´㸧Probe sequences㸦5´ FAM/3´ BHQ1㸧

CGCATGGGGTTCGGCTTCCTGTCC

Forward primer sequences

CACGGTGCGGGCATCTG

Reverse primer sequences

CCTTCCATGTGCAGCTTACTC

Primer ཬࡧ Probe ࡣࠊ50 M ࡟ㄪ〇ࡍࡿࠋὀពⅬ࣭ ࣉࣛ࢖࣐࣮࡟ࡼࡗ࡚⮳㐺࢔ࢽ࣮ࣜࣥࢢ ᗘࡀ␗࡞ࡿࡢ࡛ࠊ᮲௳᳨ウࡀᚲせࠋ࣭ 㜈್ࡢタᐃ࡟ࡼࡾ⤖ᯝࡀ኱ࡁࡃኚ໬ࡍࡿࡇ࡜࡟ὀពࡀᚲせࠋ㸫㸫㸺ཧ⪃᝟ሗ 㸼ᇵ㣴ୖΎࢆ⏝࠸ࡓ㠀◚ቯ࡛ࡢ LQYLWUR 㐀⭘⒆ᛶヨ㦂ฟ඾㸸Tateno et al. A medium hyperglycosylated podocalyxin enables noninvasive and quantitative
detection of tumorigenic human pluripotent stem cells.
Sci Rep. 2014;4:4069.
࠙ᐃ࡟ᚲせ࡞࢟ࢵࢺ࣭ᶵჾࠚ

࣭ࣄࢺES/iPS⣽⬊ࣔࢽࢱࣜࣥࢢ࢟ࢵࢺ
࣭㐲ᚰᶵ㸦1,700 x g࡛㐲ᚰࡀྍ⬟࡞㐲ᚰᶵ㸧࣭ヨ㦂⟶࣑࢟ࢧ࣮
࣭ࣉ࣮ࣞࢺ࣑࢟ࢧ࣮㸦࠶ࢀࡤዲࡲࡋ࠸㸧
࣭96࢙࢘ࣝࣉ࣮ࣞࢺὙίᶵ㸦࠶ࢀࡤዲࡲࡋ࠸㸧
࣭96࢙࢘ࣝࣉ࣮ࣞࢺ࣮ࣜࢲ࣮㸦྾ගᗘ ᐃ㸸୺Ἴ㛗 450 nmࠊ๪Ἴ㛗 600 nm ~ 650 nm㸧࠙ὀពࠚ㸺ᐃ࡟㛵ࡍࡿࡇ࡜㸼࣭ᇵᆅ஺᥮ࡋࡓ⩣᪥࡟ᇵ㣴ୖΎࢆࢧࣥࣉࣜࣥࢢࡋࠊࡑࡢᚋ࡟⣽⬊ࢆ๤ࡀࡋ࡚ࣄࢺከ⬟ᛶᖿ⣽⬊ᩘࢆ ᐃࡍࡿࠋ౛࠼ࡤᇵᆅࡀ 5 mLࠊ⣽⬊ᩘࡀ 5 × 106 cells ࡛࠶ࡗࡓሙྜࠊࢧࣥࣉࣜ
ࣥࢢࡋࡓᇵ㣴ୖΎࡢᮍศ໬⣽⬊ᩘࢆ 1 × 106 cells/mL ࡜ࡍࡿࠋ࣭ᮏ᪉ἲ࡛ࡣࠊᮍศ໬⥔ᣢᇵ㣴᮲௳ୗࡢᇵ㣴ୖΎࡢᐃ್࡟ᇶ࡙ࡃᶆ‽᭤⥺ࢆసᡂࡋࠊࡑ

ࢀࢆ୍ࡘࡢᇶ‽࡟ࡋ࡚ ᐃᑐ㇟࡜࡞ࡿヨᩱ୰ࡢᮍศ໬⣽⬊ᩘࢆ⟬ฟࡍࡿࠋ࣭⣽⬊ᰴཪࡣᇵᆅࡢ✀㢮࡞࡝ࡢᇵ㣴᮲௳࡟ࡼࡾࠊࢩࢢࢼࣝᙉᗘ࡜⣽⬊ᩘ㸦cells/mL㸧ࡢ㛵ಀࡀ␗࡞ࡿሙྜࡀ࠶ࡿࠋᶆ‽᭤⥺ࡣ⣽⬊ᰴẖཬࡧᮍศ໬⥔ᣢᇵ㣴᮲௳ẖ࡟సᡂࡍࡿࠋ
㸺࢟ࢵࢺࡢ౑⏝㸼࣭౑⏝๓ࡣ 20Υ㹼25Υ࡟ಖ⟶ࡍࡿࡇ࡜ࠋ
࣭ࣉ࣮ࣞࢺὙίᶵ࡞࡝ࢆ౑ࡗ࡚Ὑίࢆ⤊࠼ࡓᚋࡣࠊࣉ࣮ࣞࢺࢆ㏫ࡉ࡟ࡋ࡚࣮࣌ࣃ࣮ࢱ࢜ࣝ
࡞࡝࡟㍍ࡃ྇ࡁࡘࡅ࡚࢙࢘ࣝ࡟ṧࡗ࡚࠸ࡿవศ࡞Ὑίᾮࢆྲྀࡾ㝖ࡃࠋ࣭ࣉ࣮ࣞࢺࢩ࣮ࣝ௨እࡢ࢟ࢵࢺᵓᡂヨ⸆ࡣࠊ౑⏝ᚋ㏿ࡸ࠿࡟෭ⶶ࡟ᡠࡋ࡚ಖ⟶ࡍࡿࠋ㸺ヨᩱ㸦ᇵ㣴ୖΎ㸧ࡢㄪ〇ἲ㸼࣭ᐃᑐ㇟ヨᩱཬࡧᶆ‽᭤⥺సᡂ⏝ヨᩱࡣࠊᇵᆅ஺᥮ᚋ 18 ᫬㛫㹼24 ᫬㛫ᇵ㣴ࡋࡓୖΎࢆ
ࢧࣥࣉࣜࣥࢢࡍࡿࠋ

㸨඲ᇵᆅ஺᥮ࢆᇶᮏ࡜ࡋࠊࡑࡢᚋࡢᇵ㣴᫬㛫࡟ࡶᙳ㡪ࡉࢀࡿࡓࡵࠊ࡛ࡁࡿࡔࡅᇵᆅ஺᥮
ᚋࢧࣥࣉࣜࣥࢢࡲ࡛ࡢ᫬㛫ࢆ⤫୍ࡍࡿࠋ࣭ࢧࣥࣉࣜࣥࢢࡋࡓᇵ㣴ୖΎࢆ 1,700 × g 㸦3,000 rpm㸧
ࠊ10 minࠊᐊ཰ࡉࢀࡿ㐲ᚰୖΎࢆࠕヨᩱࠖ࡜ࡍࡿࠋ

㸫㸫࡛㐲ᚰࡍࡿࡇ࡜ࠋᅇ

࣭ࡍࡄ࡟ ᐃ࡟౪ࡋ࡞࠸ሙྜࡣࠊ-20Υ௨ୗ࡛෾⤖ಖᏑࡍࡿࠋ
㸺ᶆ‽᭤⥺సᡂ㸼࣭⣽⬊ᰴẖཬࡧᮍศ໬⥔ᣢᇵ㣴᮲௳ẖ࡟ᶆ‽᭤⥺ࢆసᡂࡍࡿࠋ
࣭඲ᇵᆅ஺᥮ࡋࡓ 18 ᫬㛫㹼24 ᫬㛫ᚋࡢᇵ㣴ୖΎࢆࢧࣥࣉࣜࣥࢢࡋࡓᚋࠊ⣽⬊ࢆ๤ࡀࡋ࡚
ᮍศ໬⣽⬊ᩘࢆ ᐃࡋࠊ㸺ヨᩱ㸦ᇵ㣴ୖΎ㸧ࡢㄪ〇ἲ㸼࡟ᚑࡗ࡚ᇵ㣴ୖΎ࠿ࡽヨᩱࢆㄪ〇ࡍࡿࠋ ᐃ࡟౪ࡍࡿࡲ࡛-20Υ௨ୗ࡛෾⤖ಖᏑࡍࡿ㸦ᩘᅇ⛬ᗘࡢ෾⤖⼥ゎࡣྍ⬟㸧ࠋ࣭ᐃᑐ㇟࡜࡞ࡿヨᩱ࡜ྠࡌ᪂ࡋ࠸ᇵᆅ࡛ᕼ㔘ࡋ࡚ᶆ‽᭤⥺ࢆసᡂࡍࡿࠋ᭱ึࡣ 30,000
cells/mL ࠿ࡽ 41 cells/mL ࡲ࡛ 3 ಸ࡙ࡘẁ㝵ᕼ㔘ࡋ࡚ഴྥࢆ☜࠿ࡵࠊࡑࡢᚋ࡟㐺ษ࡞⣽⬊ᩘ࠿ࡽ 2 ಸ࡙ࡘẁ㝵ᕼ㔘ࡋ᳨࡚㔞⥺ࢆసᡂࡍࡿ࡜Ⰻ࠸ࠋࡲࡓࠊᇵᆅ࡟ࡼࡗ࡚ࡣࣂࢵࢡࢢ
ࣛ࢘ࣥࢻࡀ㧗࠸ࡶࡢࡶ࠶ࡿࡓࡵࠊᚲࡎᇵᆅࡢࡳࡢ࢙࢘ࣝࡶసᡂࡍࡿࠋ

࣭ᐃẖ࡟ Strip ࡢ୍ࡘࢆᶆ‽᭤⥺⏝࡜ࡋࠊࡑࡇ࡛ᚓࡽࢀࡿᶆ‽᭤⥺࠿ࡽ ᐃᑐ㇟࡜࡞ࡿヨᩱࡢᮍศ໬⣽⬊ᩘࢆ⟬ฟࡍࡿ࡜Ⰻ࠸ࠋ

᳨࣭యᩘࡀከࡃࠊ ᐃẖ࡟ Strip ࡢ୍ࡘࢆᶆ‽᭤⥺⏝࡟౑࠺ࡇ࡜ࡀ㞴ࡋ࠸ሙྜ࡟ࡣࠊᶆ‽᭤⥺࡟౑⏝ࡍࡿ࢙࢘ࣝᩘࢆῶࡽࡍࡇ࡜ࡶ࡛ࡁࡿ㸦2~4 ࢙࢘ࣝ㸧ࠋࡓࡔࡋࠊ┤⥺㛵ಀࡀᚓࡽࢀ
ࡿ⣽⬊ᩘࢆ㑅ࡪࡇ࡜ࠋ
࠙᧯సࠚ
㸺‽ഛ㸼
࣭౑⏝ࡍࡿ๓࡟ࠊrBC2LCN ᅛ┦໬ࣉ࣮ࣞࢺࠊ㝜ᛶࢥࣥࢺ࣮ࣟࣝࠊ㝧ᛶࢥࣥࢺ࣮ࣟࣝࠊᕼ㔘ᾮࠊὙίᾮ㸦10 ×㸧ࠊⓎⰍ೵Ṇᾮࠊࣉ࣮ࣞࢺࢩ࣮ࣝࢆᐊ ࡟ࡍࡿ㸦HRP ᶆ㆑ᢠయ⁐ᾮཬࡧ TMB ⁐ᾮ௨እࡢヨ⸆㸧ࠋ࣭Ὑίᾮ㸦10 ×㸧ࢆᐊ ࡢ⵨␃Ỉ࡛ 10 ಸᕼ㔘ࡍࡿࠋὙίᾮ㸦1 ×㸧ࡣ 1-Strip ࠶ࡓࡾᑡ࡞ࡃ
࡜ࡶ 40 mL ᚲせ࡜࡞ࡿ㸦350 L/࢙࢘ࣝ×Ὑί 12 ᅇ × 8 ࢙࢘ࣝ㸧ࠋ ᐃᩘ㸦౑⏝ࡍࡿ Stripᩘ㸧࡟࠶ࢃࡏ࡚ㄪ〇ࡍࡿࠋࡓࡔࡋࠊࣉ࣮ࣞࢺὙίᶵࢆ౑࠺ሙྜࡣࠊᶵᲔࡢࢭࢵࢸ࢕ࣥࢢ࡟せࡍࡿᾮ㔞ࢆ⪃៖ࡋከ┠࡟ㄪ〇ࡍࡿࡇ࡜ࠋ
࣭཯ᛂࡢᡂྰࢆ☜࠿ࡵࡿࡓࡵࡢ㝧ᛶࢥࣥࢺ࣮ࣟࣝࡣࠊ౑⏝┤๓࡟ᕼ㔘ᾮ࡛ 40 ಸᕼ㔘ࡍࡿ㸦ᕼ㔘ᾮ 195 L ࡟㝧ᛶࢥࣥࢺ࣮ࣟࣝ 5 L ࢆῧຍᚋ࣎ࣝࢸࢵࢡࢫ࡛ΰྜࡋ࡚ࠊ50 L/࢙࡛࢘ࣝ✵࠸࡚࠸ࡿ࢙࢘ࣝ࡟ῧຍࡍࡿ㸧ࠋ࣭㝜ᛶࢥࣥࢺ࣮ࣟࣝࡣࠊᕼ㔘ࡏࡎࡑࡢࡲࡲ࢙࢘ࣝ࡟ῧຍࡍࡿ
࣭HRP ᶆ㆑ᢠయ⁐ᾮࡣࠊ౑⏝┤๓࡟ᕼ㔘ᾮ࡛ 20 ಸᕼ㔘ࡋ࡚ᚲせ㔞㸦50 L/࢙࢘ࣝ × ࢙࢘ࣝᩘ㸧ࢆㄪ〇ࡍࡿࡇ࡜ࠋᚲせ㔞ࢆྲྀࡾฟࡋࡓᚋࡢ HRP ᶆ㆑ᢠయ⁐ᾮࡣ㏿ࡸ࠿࡟෭ⶶ࡟
ᡠࡍࡇ࡜ࠋ
࣭TMB ⁐ᾮࡣࠊⓎⰍ཯ᛂࡢ 20 ศ๓㹼30 ศ๓࡟ࠊᚲせ㔞㸦50 L/࢙࢘ࣝ × ࢙࢘ࣝᩘ㸧ࢆ⁛⳦ࡉࢀࡓ᪂ࡋ࠸ࢳ࣮ࣗࣈ࡟ศࡅ࡚ࠊ౑⏝ࡍࡿࡲ࡛ගࢆ㑊ࡅ࡚ᐊ ࡛ಖ⟶ࡍࡿࡇ࡜ࠋᚲせ㔞ࢆྲྀࡾฟࡋࡓᚋࡢ TMB ⁐ᾮࡣ㏿ࡸ࠿࡟෭ⶶ࡟ᡠࡍࡇ࡜ࠋ

㸫㸫



㸺

ᐃᡭ㡰㸼

(1) rBC2LCN ᅛ┦໬ࣉ࣮ࣞࢺࡀᐊ ࡟࡞ࡗࡓࡇ࡜ࢆ☜ㄆࡋࡓᚋࠊ⿄࠿ࡽࣉ࣮ࣞࢺࢆྲྀࡾฟࡋࠊ ᐃ࡟౑⏝ࡋ࡞࠸ Strip ࢆࣉ࣮ࣞࢺᯟ࠿ࡽእࡋ࡚⿄࡟ᡠࡋࠊࢳࣕࢵࢡࢆ㛢ࡌ࡚෭ⶶ࡟ಖ⟶ࡍࡿࠋ
(2) ࣉ࣮ࣞࢺᯟࡢ࣍ࣝࢲ࣮ࢆ㛢ࡌ࡚ Strip ࢆᅛᐃࡋࠊὙίᾮ㸦× 1㸧
ࠊ350 L/࢙࡛࢘ࣝ㸱ᅇὙίࡍࡿࠋࡑࡢᚋࠊࣉ࣮ࣞࢺࢆ㏫ࡉ࡟ࡋ࡚࣮࣌ࣃ࣮ࢱ࢜ࣝ࡞࡝࡟㍍ࡃ྇ࡁࡘࡅ࡚࢙࢘ࣝ
࡟ṧࡗ࡚࠸ࡿὙίᾮࢆྲྀࡾ㝖ࡃࠋ(3) ᶆ‽᭤⥺⏝ヨᩱࠊ ᐃᑐ㇟ヨᩱࠊᚲせ࡞ࡽࡤ㝜ᛶࢥࣥࢺ࣮ࣟࣝཬࡧ㝧ᛶࢥࣥࢺ࣮ࣟࣝ
ࢆࠊྛࠎ50 L/࢙࢘ࣝῧຍࡋࠊࣉ࣮ࣞࢺ࣑࢟ࢧ࣮࡞࡝࡛㍍ࡃ᧠ᢾࡋࡓᚋࠊࣉ࣮ࣞࢺࢩ࣮
ࣝࢆ㈞ࡗ࡚ᐊ ࡛㸯᫬㛫㟼⨨཯ᛂࡉࡏࡿࠋ
(4) ࣉ࣮ࣞࢺࢩ࣮ࣝࢆࡣࡀࡋࠊὙίᾮ㸦× 1㸧
ࠊ350 L/࢙࡛࢘ࣝ㸱ᅇὙίࡍࡿࠋࡑࡢᚋࠊࣉ
࣮ࣞࢺࢆ㏫ࡉ࡟ࡋ࡚࣮࣌ࣃ࣮ࢱ࢜ࣝ࡞࡝࡟㍍ࡃ྇ࡁࡘࡅ࡚࢙࢘ࣝ࡟ṧࡗ࡚࠸ࡿὙίᾮ
ࢆྲྀࡾ㝖ࡃࠋ
(5) 20 ಸᕼ㔘ࡋࡓ HRP ᶆ㆑ᢠయ⁐ᾮࢆࠊ50 L/࢙࢘ࣝῧຍࡋࣉ࣮ࣞࢺ࣑࢟ࢧ࣮࡞࡝࡛㍍ࡃ
᧠ᢾࡋࡓᚋࠊࣉ࣮ࣞࢺࢩ࣮ࣝࢆ㈞ࡗ࡚ᐊ ࡛㸯᫬㛫㟼⨨཯ᛂࡉࡏࡿࠋ
(6) ࣉ࣮ࣞࢺࢩ࣮ࣝࢆ๤ࡀࡋࠊὙίᾮ㸦1 ×㸧
ࠊ350 L/࢙࡛࢘ࣝ 6 ᅇὙίࡍࡿࠋࡑࡢᚋࠊࣉ
࣮ࣞࢺࢆ㏫ࡉ࡟ࡋ࡚࣮࣌ࣃ࣮ࢱ࢜ࣝ࡞࡝࡟㍍ࡃ྇ࡁࡘࡅ࡚࢙࢘ࣝ࡟ṧࡗ࡚࠸ࡿὙίᾮ
ࢆྲྀࡾ㝖ࡃࠋ
(7) TMB ⁐ᾮࢆࠊ50 L/࢙࢘ࣝῧຍࡋࠊࣉ࣮ࣞࢺ࣑࢟ࢧ࣮࡞࡝࡛㍍ࡃ᧠ᢾࡋࡓᚋࠊᐊ ࡛
30 ศ㛫㟼⨨཯ᛂࡉࡏࡿ㸦࢔࣑ࣝ࣍࢖ࣝ࡞࡝࡛ୖ࠿ࡽ࢝ࣂ࣮ࡋ࡚ගࢆ㑊ࡅࡿ㸧(8) ⓎⰍ೵Ṇᾮࢆࠊ50 L/࢙࢘ࣝῧຍࡋࠊ㍍ࡃ᧠ᢾࡋ࡚཯ᛂࢆ೵Ṇࡉࡏࠊࣉ࣮ࣞࢺ࣮ࣜࢲ࣮
࡛྾ගᗘ㹙୺Ἴ㛗 450 nmࠊ๪Ἴ㛗 620 nm㹼650 nm㹛ࢆ ᐃࡍࡿࠋἻ࡞࡝ࡀ⏕ࡌ࡚࠸ࡿሙྜࡣࠊࢳࢵࣉࡢඛ࡞࡝࡛ᾘࡋ࡚࠿ࡽ ᐃࡍࡿࠋ(9) ᶆ‽᭤⥺࡟ᇶ࡙࠸࡚ࠊ ᐃᑐ㇟࡜࡞ࡿヨᩱ୰ࡢᮍศ໬⣽⬊ᩘࢆ⟬ฟࡍࡿࠋ㸨㝧ᛶࢥࣥࢺ࣮ࣟࣝࢆ౑⏝࡟࡞ࡗࡓሙྜࡣࠊࡑࡢ྾ගᗘࡀ 0.5 ௨ୖ࡛࠶ࡿࡇ࡜ࠊ㝜ᛶࢥࣥࢺ࣮ࣟࣝࢆ౑⏝ࡋࡓሙྜࡣࡑࡢ྾ගᗘࡀ 0.15 ᮍ‶࡛࠶ࡿࡇ࡜ࢆ☜ㄆࡍࡿࡇ࡜ࠋ
᧯సᡭ㡰㸦ࣇ࣮ࣟࢳ࣮ࣕࢺ㸧rBC2LCN ᅛ┦໬ࣉ࣮ࣞࢺЎὙί㸱ᅇᶆ‽᭤⥺⏝ヨᩱࠊ ᐃᑐ㇟ヨᩱࠊሙྜ࡟ࡼࡾ㝜ᛶཬࡧ㝧ᛶࢥࣥࢺ࣮ࣟࣝࢆ 50 L/࢙࢘ࣝῧຍЎ᧠ᢾࠊᐊ ࠊ㸯᫬㛫཯ᛂ㸦㟼⨨㸧ЎὙί㸱ᅇHRP ᶆ㆑ᢠయ⁐ᾮ㸦20 ಸᕼ㔘㸧ࢆ 50 L/࢙࢘ࣝῧຍ

㸫㸫Ў᧠ᢾࠊᐊ ࠊ㸯᫬㛫཯ᛂ㸦㟼⨨㸧ЎὙί㸴ᅇ
TMB ⁐ᾮࢆ 50 L/࢙࢘ࣝῧຍ
Ў᧠ᢾࠊᐊ ࠊ30 ศ㛫཯ᛂ㸦㟼⨨ࠊ㐽ග㸧ⓎⰍ೵Ṇᾮࢆ 50 L/࢙࢘ࣝῧຍЎ᧠ᢾ྾ගᗘ ᐃ㸦୺Ἴ㛗 450 nmࠊ๪Ἴ㛗 600㹼650 nm㸧








㸫㸫㸺ཧ⪃᝟ሗ 㸼ΰᅾࡍࡿᮍศ໬ (6L36 ⣽⬊ࡢ᳨ฟἲ࡜ࡋ࡚ࡢ (VVHQWLDO/1 ᇵ㣴ቑᖜἲฟ඾㸸Tano et al. A novel in vitro method for detecting undifferentiated human pluripotent stem cells
as impurities in cell therapy products using a highly efficient culture system
PLoS ONE. 2014;9:e110496.
࠙᪉ἲࠚ
1. ࣄࢺ iPS ⣽⬊࠿ࡽ㛫ⴥ⣔ᖿ⣽⬊࡬ࡢศ໬㏵୰࡛ṧᏑࡍࡿᮍศ໬ iPS ⣽⬊ࡢ᳨ฟ
1.1 laminin-521㸦LN521㸧ࢥ࣮ࢸ࢕ࣥࢢࣉ࣮ࣞࢺࡢస〇 PBS ࡛ 20 ȝg/mL ࡟ᕼ㔘ࡋࡓ LN521 ࢆᇵ㣴⏝ࣉ࣮ࣞࢺ࡟ῧຍ㸦1 mL / 10 cm2㸧ࡋࠊ37Υ࡛㸰᫬㛫௨ୖ࢖࣮ࣥ࢟ࣗ࣋ࢺࡍࡿࠋࡑࡢᚋ LN521 ࢆᅇ཰ࡋࠊPBS ࡛ὙίࡍࡿࠋEssential 8ᇵᆅ୍࡛ᗘὙࡗࡓᚋࠊEssential 8 ᇵᆅࢆῧຍ㸦2 mL / 10 cm2㸧ࡋࠊ⣽⬊ࢆ᧛✀ࡍࡿࡲ࡛37Υ࡛࢖࣮ࣥ࢟ࣗ࣋ࢺࡍࡿࠋ
1.2 㝧ᛶᑐ↷⣽⬊ࡢㄪ〇 ศ໬⣽⬊࡜ࡋ࡚ࣄࢺ㦵㧊⏤᮶㛫ⴥ⣔ᖿ⣽⬊㸦hMSC㸧ࢆ⏝ពࡋࠊEssential 8 ᇵᆅ୰࡟ศᩓ
ࡉࡏࡿࠋࡇࡢ୰࡟ࠊศ໬ㄏᑟ࡟౑⏝ࡋࡓඖࡢ iPS ⣽⬊ᰴࢆࠊࢩࣥࢢࣝࢭࣝࡢ≧ែ࡟ࡋ࡚
Essential 8 ᇵᆅ୰࡟ศᩓࡉࡏࡓᚋࠊࢫࣃ࢖ࢡࡍࡿࠋ
㸦౛࠼ࡤࠊiPS ⣽⬊ࡢΰᅾ⋡ࡀ 1ࠊ0.1ࠊ
0.01%ࡢሙྜࠊ1 × 105 ಶࡢ MSC ୰࡟ 1 × 103ࠊ 1 × 102ࠊ 1 × 10 ಶࡢ๭ྜ࡛ iPS ⣽⬊ࢆࡑࢀࡒࢀࢫࣃ࢖ࢡࡉࡏࡿࠋࡲࡓ iPS ⣽⬊ࡢΰᅾ⋡ࡀ 0.001%ࡢሙྜࠊ6 × 105 ಶࡢ hMSC ୰࡟㸴ಶࡢ๭ྜ࡛ iPS ⣽⬊ࢆࢫࣃ࢖ࢡࡉࡏࡿࠋ
㸧ศ໬⣽⬊࡜ࣄࢺ iPS ⣽⬊ࢆࡼࡃΰࡐࡓᚋࠊ1.1 ࡛‽ഛࡋࡓ LN521 ࢥ࣮ࢸ࢕ࣥࢢࣉ࣮ࣞࢺ࡟ῧຍࡋࠊ37Υ 5%CO2 ࡛ᇵ㣴ࡍࡿࠋ㸦hMSC ࡀ 1 × 105 ࡢ
ሙྜࡣ 35 mm ࢹ࢕ࢩࣗ㸦ཪࡣ 6 ࢙࢘ࣝࣉ࣮ࣞࢺ㸧ࠊ6 × 105 ࡢሙྜࡣ 100 mm ࢹ࢕ࢩࣗࢆ౑
⏝ࠋ㸧ᇵ㣴ࢆጞࡵ࡚࠿ࡽ㸰᪥ᚋࡼࡾẖ᪥ᇵᆅ஺᥮ࡍࡿࠋ┠ど࡛ࡁࡿࢥࣟࢽ࣮ࡀᙧᡂࡉࢀࡿࡲ
࡛ࡢ㛫ࡣࠊ࢔ࢫࣆ࣮ࣞࢺࢆ౑⏝ࡏࡎࠊࢳࢵࣉཪࡣࣆ࣌ࢵࢺ࡛ᇵᆅࢆᅇ཰ࡍࡿࠋ
1.3 ࢸࢫࢺࢧࣥࣉࣝࡢㄪ〇 ࣄࢺ iPS ⣽⬊࠿ࡽศ໬ㄏᑟࡋࡓ⣽⬊ࢆ Accutase ࡛๤ࡀࡋࠊEssential 8 ᇵᆅ୰࡟ศᩓࡉࡏ
ࡿࠋ1.1 ࡛‽ഛࡋࡓ LN521 ࢥ࣮ࢸ࢕ࣥࢢࣉ࣮ࣞࢺ࡟ῧຍࡋࠊ37Υ 5%CO2 ࡛ᇵ㣴ࡍࡿࠋᇵᆅ஺᥮ࡢ᪉ἲࡣ 1.2 ࡜ྠᵝࠋ
1.4 ṧᏑᮍศ໬ iPS ⣽⬊ࡢ᳨ฟ ᇵ㣴㛤ጞ࠿ࡽ࠾ࡼࡑ 1 㐌㛫௨ෆ࡟ṧᏑ iPS ⣽⬊ࡀቑṪࡋࠊࢥࣟࢽ࣮ࢆᙧᡂࡍࡿࠋࡇࡢࢥ
ࣟࢽ࣮ࡢ᭷↓ࢆ☜ㄆࡋࠊᩘࢆィ ࡍࡿࠋᙧᡂࡉࢀࡓࢥࣟࢽ࣮ࡀᮍศ໬ iPS ⣽⬊࡟⏤᮶ࡍࡿࡇ࡜ࡢ☜ㄆ࡜ࡋ࡚ࠊTRA-1-60 ࡞࡝ࡢᮍศ໬࣐࣮࣮࢝࡟ᑐࡍࡿᢠయ࡛ච␿ᰁⰍࡍࡿࠋ ṧᏑࡢ᭷↓ࢆุ᩿ࡍࡿ࡟ࡣࠊ㝧ᛶᑐ↷࡛ṧᏑ iPS ⣽⬊ࡢ᳨ฟឤᗘࢆ☜ㄆࡋ࡚࠾ࡃᚲせࡀ㸫㸫࠶ࡿࠋࡲࡓࠊᮏ᪉ἲ࡛ࡣࠊ㝧ᛶᑐ↷᳨࡛ฟࡉࢀࡿࢥࣟࢽ࣮ᩘ࡜ẚ㍑ࡍࡿࡇ࡜࡛ࠊ࠾࠾ࡼࡑ
ࡢṧᏑ⋡ࢆぢ✚ࡶࡿࡇ࡜ࡀ࡛ࡁࡿࠋ

㸫㸫㸺ཧ⪃᝟ሗ 㸼ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊ࡢ᳨ฟἲ࡜ࡋ࡚ࡢ LQYLYR 㐀⭘⒆ᛶヨ㦂ฟ඾㸸Kusakawa et al. Characterization of in vivo tumorigenicity tests using severe immunodeficient
NOD/Shi-scid IL2RȖnull mice for detection of tumorigenic cellular impurities in human cellprocessed therapeutic products.
Regenerative Therapy. 2015;1:30-37.
࠙᪉ἲࠚ
1. NOG ࣐࢘ࢫࢆ⏝࠸ࡓ㐀⭘⒆ᛶヨ㦂
1.1 ⣽⬊ᇵ㣴 ⛣᳜⣽⬊࡜ࡋ࡚ࠊᙧ㉁㌿᥮⣽⬊࡛࠶ࡿ HeLa ⣽⬊ࢆࠊṇᖖ⣽⬊࡛࠶ࡿࣄࢺ㦵㧊⏤᮶㛫ⴥ⣔ᖿ⣽⬊㸦hMSC㸧ࢆ⏝࠸ࡿࠋᇵᆅࡣࠊHeLa ⣽⬊ࡢᇵ㣴࡛ࡣ 10%FBS ྵ᭷ Eagle’s minimum
essential medium㸦MEM㸧ᇵᆅࢆ⏝࠸ࠊhMSC ࡢᇵ㣴࡛ࡣ Mesenchymal Stem Cell Growth Medium
㸦MSCGM㸧ᇵᆅࢆ⏝࠸ࡿࠋ
1.2 ⣽⬊⛣᳜࡜⭘⒗ᙧᡂࡢほᐹ
1.2.1 ࣇࣛࢫࢥࡢ㠃✚ࡢ 80㸣ࢆ⣽⬊ࡀそ࠸ᑾࡃࡋࡓ≧ែ࡟㐩ࡋࡓྛ⣽⬊ࢆ 0.25%ࢺࣜࣉࢩࣥ-EDTA ⁐ᾮ࡛๤ࡀࡋࠊ௨ୗࡢ⃰ᗘࡢ⣽⬊ᠱ⃮ᾮࢆㄪ〇ࡍࡿࠋ1) 1 ×106 ಶࡢ hMSC ࡟ 10 ಶ
㸦0.001%㸧
ࠊ1 × 102 ಶ㸦0.01%㸧
ࠊ1 × 103 ಶ㸦0.1%㸧
ࠊ1 × 104 ಶ㸦1%㸧ಶࡢ HeLa ⣽⬊ࢆΰධࡍࡿࠋ2) 1 × 107 ಶࡢ hMSC ࡟ 10 ಶ㸦0.0001%㸧ࠊ1 × 102 ಶ㸦0.001%㸧ࠊ1 × 104 ಶ㸦0.1%㸧ಶࡢ HeLa ⣽⬊ࢆΰධࡍࡿࠋ⛣᳜⏝ࡢ⣽⬊ᠱ⃮ᾮࡣࠊ100 L ୰࡟ୖグࡢ㔞ࡢ⣽⬊ࢆྵࡴࡼ࠺
࡟ࠊ10%FBS ྵ᭷ MEM ᇵᆅ࡜࣐ࢺࣜࢤࣝࢆ 1:1 ࡢ๭ྜ࡛ྵࡴᇵᆅ୰࡟ㄪ〇ࡋࠊ⛣᳜ࡢ┤๓ࡲ࡛ịୖ࡟⨨࠸࡚࠾ࡃࠋ
1.2.2 6~8 㐌㱋ࡢ㞝ᛶ NOG ࣐࢘ࢫ㸦NOD/Shi-scid ,/5ȖKO Jic㸧ࡢ⫼㒊⓶ୗ࡟ࠊ25G 㔪௜ࡁࡢ 1 mL ࢩࣜࣥࢪࢆ⏝࠸࡚ 100 L ⛣᳜ࡍࡿࠋ㸯⩌࠶ࡓࡾ㸴༉௨ୖࢆ⏝࠸ࡿࠋ
1.2.3 ẖ㐌ࠊどデཬࡧゐデ࡟ࡼࡗ࡚⭘⒗ᙧᡂࡢ᭷↓ࢆ☜ㄆࡍࡿ㸦16 㐌㛫㸧ࠋ⭘⒗ࡢᙧᡂࡀ☜ㄆࡉࢀࡓࡽࠊࣀࢠࢫࢆ⏝࠸㛗ᚄ࡜▷ᚄࡢ㛗ࡉࢆィ ࡍࡿࠋ⭘⒗య✚㸦mm3㸧ࡣࠊ㛗ᚄ㸦mm㸧
×▷ᚄ 2㸦mm㸧2×1/2 ࡢィ⟬ᘧ࡛ồࡵࡿࠋ⭘⒗㔜㔞㸦ẚ㔜ࢆ㸯࡜ࡋ࡚య✚ࡼࡾィ⟬㸧ࡀయ㔜ࡢ
10%ࢆ㉸࠼ࡿ኱ࡁࡉ࡟㐩ࡋࡓሙྜཪࡣ 16 㐌ࢆ⤒㐣ࡋࡓሙྜࠊ඲࡚ࡢື≀ࢆᏳᴦṚࡉࡏ๗᳨ࡋࠊ⑓⌮Ꮫⓗホ౯ࡢࡓࡵ࡟༢㞳ࡋࡓ⭘⒗⤌⧊ࢆ 10%୰ᛶ⦆⾪࣐࣍ࣝࣜࣥ⁐ᾮ࡟ಖᏑࡍࡿࠋ
1.2.4 ྛ⣽⬊⃰ᗘ⩌࡟ࡘ࠸࡚ࠊ⭘⒗ᙧᡂ㢖ᗘ㸦⭘⒗ᙧᡂࡀ☜ㄆ࡛ࡁࡓ༉ᩘ㸭⛣᳜༉ᩘ㸧ࢆồ
ࡵࠊSpearman-Karber ἲ࡟ᇶ࡙࠸࡚ࠊ50%⭘⒆ᙧᡂ⣽⬊⃰ᗘ㸦TPD50㸧ࢆ⟬ฟࡍࡿࠋ㸫㸫

1.3 ṇᖖ⣽⬊୰ࡢ㐀⭘⒆ᛶ⣽⬊ΰᅾࡢ᭷↓ࡢホ౯ 㝧ᛶᑐ↷⣽⬊ࡢ⤖ᯝ࠿ࡽࠊ㸯༉ࡢ࣐࢘ࢫ࡟࠾ࡅࡿ⭘⒗ᙧᡂࡀ㉳ࡇࡽ࡞࠸☜⋡㸦ഇ㝜ᛶ⋡㸧x㸦㸻1 - ⭘⒗ᙧᡂ㢖ᗘ㸧ࡀᚓࡽࢀࡿࠋn ༉ࡢ࣐࢘ࢫ࡟⛣᳜ࡋ࡚඲ࡃ⭘⒗ᙧᡂࡀほᐹࡉࢀ࡞࠸
☜⋡ y ࡣࠊy = xn ࡜⾲ࡉࢀࡿࠋn = log y / log x ࡜࠸࠺ᘧࡀᑟ࠿ࢀࠊチᐜ࡛ࡁࡿഇ㝜ᛶ⋡࡟ᛂࡌࡓヨ㦂࡟ᚲせ࡞ື≀ᩘࢆ⟬ฟࡍࡿࡇ࡜ࡀྍ⬟࡛࠶ࡿࠋ౛࠼ࡤࠊ10 ಶࡢ HeLa ⣽⬊ࢆΰධࡉࡏࡓ hMSC 1 × 107 ಶ㸦HeLa ⣽⬊ΰᅾ⋡ 0.0001%㸧ࢆ⛣᳜ࡋࡓ᫬ࡢ⭘⒗ᙧᡂ⋡ࡀ 17%࡜࠸࠺
⤖ᯝࡀᚓࡽࢀ࡚࠸ࡓሙྜࠊHeLa ⣽⬊┦ᙜࡢ㐀⭘⒆ᛶ⣽⬊ࡀ 1/106 ࡢ๭ྜ࡛ΰᅾࡍࡿ⣽⬊ࢆ⛣᳜ࡋࡓ㸯༉ࡢ࣐࢘ࢫ࡟࠾࠸࡚⭘⒗ࡀᙧᡂࡉࢀ࡞࠸☜⋡㸦ഇ㝜ᛶ⋡㸧x ࡣ 0.83 ࡜ࡍࡿࠋ1%ࡢ☜⋡࡛ഇ㝜ᛶࡢุᐃࡋ࡚ࡋࡲ࠺ࡇ࡜ࢆチᐜ࡛ࡁࡿ࡜ࡍࡿ࡜ࠊHeLa ⣽⬊┦ᙜࡢ㐀⭘⒆ᛶ⣽⬊ࡀ 1/106 ࡢ๭ྜ࡛ΰᅾࡋ࡚࠸࡞࠸ࡇ࡜ࢆ♧ࡍ࡟ࡣࠊ25 ༉㸦= log 0.01 / log 0.83㸧ࡢື≀ࡑࢀ
ࡒࢀ࡟ 1 × 107 ಶࢆ⛣᳜ࡋࠊ㸯༉ࡶ⭘⒗ᙧᡂࡀ࡞࠸ࡇ࡜ࡀ☜ㄆ࡛ࡁࢀࡤࡼ࠸ࠋ

㸫㸫㸺ཧ⪃᝟ሗ 㸼ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊ࡢ᳨ฟἲ࡜ࡋ࡚ࡢࢹࢪࢱࣝ㌾ᐮኳࢥࣟࢽ࣮ᙧᡂヨ㦂ฟ඾㸸Kusakawa et al. Ultra-sensitive detection of tumorigenic cellular impurities in human cellprocessed therapeutic products by digital analysis of soft agar colony formation.
Sci Rep. 2015;5:17892
࠙᪉ἲࠚ
1. ⣽⬊ᇵ㣴ཬࡧヨ⸆㢮 ᙧ㉁㌿᥮⣽⬊࡜ࡋ࡚ HeLa ⣽⬊ࢆࠊṇᖖ⣽⬊࡜ࡋ࡚ࣄࢺ㦵㧊⏤᮶㛫ⴥ⣔ᖿ⣽⬊㸦hMSC㸧ࢆ⏝࠸ࡿࠋ㏻ᖖࡢ HeLa ⣽⬊ࡢ⥔ᣢᇵ㣴࡟ࡣ 10% FBS ྵ᭷ MEM ᇵᆅࢆࠊhMSC ࡢ⥔ᣢᇵ㣴࡟ࡣ Mesenchymal Stem Cell Growth Medium㸦MSCGM㸧ᇵᆅࢆ⏝࠸ࡿࠋ㌾ᐮኳᇵ㣴⏝ᇵᆅ࡜ࡋ࡚ࠊDMEM ⢊ᮎᇵᆅ㸦ࣇ࢙ࣀ࣮ࣝࣞࢵࢻࣇ࣮ࣜ㸧ࢆ⏝࠸࡚ㄪ〇ࡋࡓ 10% FBS ྵ᭷ 1 ×
DMEM ᇵᆅཬࡧ 20% FBS ྵ᭷ 2 × DMEM ᇵᆅࠊప⼥Ⅼ࢔࣮࢞ࣟࢫ SeaPlaque ࡜⁛⳦Ỉ࡛ㄪ〇ࡋࡓ 1.2%࢔࣮࢞ࣟࢫ⁐ᾮࢆ౑⏝ࡍࡿࠋ⏕⣽⬊ᰁⰍ⏝⺯ගヨ⸆࡜ࡋ࡚ࠊMitoTracker Red
CMXRos ཬࡧ Hoechst 33342 ࢆ⏝࠸ࡿࠋ96 ࢙࢘ࣝࣉ࣮ࣞࢺࡣࠊᗏ㠃ࡢ⣲ᮦࡣࠊࣉࣛࢫࢳࢵࢡ
࠿ࡘ⣽⬊ᇵ㣴ฎ⌮ࡀ࡞ࡉࢀ࡚࠸࡞࠸ࡶࡢࡀᮃࡲࡋࡃࠊࡉࡽ࡟࢙࢘ࣝഃ㠃ࡀ㯮ࡢࡶࡢࡀ⏬ീゎᯒ࡟㐺ࡋ࡚࠸ࡿࠋࢸࣛࢧ࢟ࣉ࣮ࣞࢺࠊ0.25%ࢺࣜࣉࢩࣥ-EDTA ⁐ᾮࠊ4% PFA ⁐ᾮࠊPBSࠊ
Buffer QG㸦ᐮኳᇵᆅ⁐ゎ⏝ࣂࢵࣇ࢓࣮㸧ࠊࣁ࢖ࢥࣥࢸࢶ࢖࣓࣮ࢪࣥࢢࢩࢫࢸ࣒ࢆ౑⏝ࡍࡿࠋ
2. ヨ㦂᪉ἲ
2.1 ㌾ᐮኳࢥࣟࢽ࣮ᙧᡂヨ㦂 ୗᅗ࡟♧ࡍࡼ࠺࡞ᇵᆅ⤌ᡂ࡛⣽⬊ࡢ㸱ḟඖᇵ㣴ࢆ⾜࠺ࠋᇵᆅᒙ 100 L
㸦10% FBS ྵ᭷ 1 × DMEM ᇵᆅ㸧
⣽⬊/㌾ᐮኳᒙ 75 L
㸦10% FBS ྵ᭷ 1 × DMEM ᇵᆅࠊ0.4%࢔࣮࢞ࣟࢫ
ྵ㸧ᗏ㒊ᐮኳᇵᆅᒙ 50 L
㸦10% FBS ྵ᭷ 1 × DMEM ᇵᆅࠊ0.6%࢔࣮࢞ࣟࢫ
ྵ㸧ᅗ㸬㌾ᐮኳᇵ㣴㸦96 ࢙࢘ࣝࣉ࣮ࣞࢺ 1 ࢙࢘ࣝࡢ᩿㠃ᅗ㸧 ‽ഛ࡜ࡋ࡚ࠊ10% FBS ྵ᭷ 1 × DMEM ᇵᆅ࡜ 20% FBS ྵ᭷ 2×DMEM ᇵᆅࢆࡑࢀࡒࢀ
37Υ࡟ ࡵ࡚࠾ࡃࠋ1.2%࢔࣮࢞ࣟࢫ⁐ᾮࡣ㟁Ꮚࣞࣥࢪ࡛⁐ゎࡋࠊ37Υ࡟ಖࡗ࡚࠾ࡃࠋ ᗏ㒊ᐮኳᇵᆅᒙࡢㄪ〇㸸20% FBS ྵ᭷ 2 × DMEM ᇵᆅ࡜ 1.2%࢔࣮࢞ࣟࢫ⁐ᾮࢆ 1:1 ࡢ๭ྜ࡛ΰࡐࠊ96 ࢙࢘ࣝࣉ࣮ࣞࢺࡢྛ࢙࢘ࣝ࡟ 50 l ࡎࡘศὀࡋࠊࣉ࣮ࣞࢺࢆ෭ⶶᗜ㸦㸲Υ㸧࡟⛣ࡋ࡚ 30 ศ㛫ᅛ໬ࡉࡏࡿࠋ
㸫㸫 ⣽⬊/㌾ᐮኳᒙࡢㄪ〇㸸⣽⬊ࡣࠊ0.25%ࢺࣜࣉࢩࣥ-EDTA ⁐ᾮ࡛๤ࡀࡋࠊ10% FBS ྵ᭷ 1 ×
DMEM ᇵᆅࢆ⏝࠸࡚ᵝࠎ࡞⃰ᗘ࡟ㄪ〇ࡋ࡚࠾ࡃ㸦౛࠼ࡤࠊ1 ࢙࢘ࣝ㎶ࡾ 1 x 104 ಶࡢ⣽⬊ࢆ᧛✀ࡍࡿሙྜࠊ4 × 105 ಶ/mL ࡢ⃰ᗘ࡛ᠱ⃮ᾮࢆㄪ〇ࡋ࡚࠾ࡃЍ1 x 104 ಶ/25 L㸧ࠋ10% FBS
ྵ᭷ 1 × DMEM ᇵᆅ࡛ㄪ〇ࡋࡓ⣽⬊ᠱ⃮ᾮࠊ20%FBS ྵ᭷ 2 × DMEM ᇵᆅࠊ1.2%࢔࣮࢞ࣟࢫ⁐ᾮࢆ 1:1:1 ࡢ๭ྜ࡛ΰࡐࠊ96 ࢙࢘ࣝࣉ࣮ࣞࢺࡢᅛ໬ࡋࡓᗏ㒊ᐮኳᇵᆅᒙୖ࡟ 75 L ࡎࡘศὀࡋࠊࣉ࣮ࣞࢺࢆ෭ⶶᗜ㸦㸲Υ㸧࡟⛣ࡍ㸦15 ศ㛫㸧ࠋ ᇵᆅᒙ㸸10% FBS ྵ᭷ 1 × DMEM ᇵᆅ 100 L ࢆ⣽⬊/㌾ᐮኳᒙୖ࡟ῧຍࡍࡿࠋᇵᆅ஺᥮
ࡣ 3~4 ᪥࡟୍ᗘࡢ㢖ᗘ࡛⾜࠸ࠊ37Υࠊ5% CO2 ⃰ᗘ⎔ቃࡢ࢖࣮ࣥ࢟ࣗ࣋ࢱ࣮࡛ 30 ᪥㛫ᇵ㣴ࡍࡿࠋ2.2 ࣁ࢖ࢥࣥࢸࣥࢶ࢖࣓࣮ࢪࣥࢢࢩࢫࢸ࣒ࢆ⏝࠸ࡓࢥࣟࢽ࣮ࡢ⏬ീゎᯒ ᰁⰍ㸸 ᪥㛫ࡢᇵ㣴ᚋࠊྛ࢙࢘ࣝ࠿ࡽᇵᆅ  / ࢆࣆ࣌ࢵࢺ࡛ྲྀࡾ㝖ࡁࠊ⏕⣽⬊ᰁⰍ
ヨ⸆ࢆྵࡴ )%6 ྵ᭷ ð'0(0 ᇵᆅ㸦JP/+RHFKVWࠊQ00LWR7UDFNHU
5HG&0;5RV㸧ࢆ / ࡎࡘῧຍࡋ㸦+RHFKVW ࡢ᭱⤊⃰ᗘࠊJP/㸹0LWR7UDFNHU
5HG&0;5RV ࡢ᭱⤊⃰ᗘࠊQ0㸧ࠊΥࠊ&2 ⃰ᗘ⎔ቃࡢ࢖࣮ࣥ࢟ࣗ࣋ࢱ࣮࡛㸯᫬㛫ᇵ㣴ࡍࡿࠋᅛᐃ㸸⏕⣽⬊ᰁⰍヨ⸆ࢆྵࡴ 10% FBS ྵ᭷ 1 × DMEM ᇵᆅࢆࣆ࣌ࢵࢺ࡛ྲྀࡾ㝖ࡁ㸦PBS ࢆ 100 L ῧຍࡋࡓᚋࠊ୍⥴࡟ྲྀࡾ㝖ࡃ㸧
ࠊ4% PFA ⁐ᾮࢆ 125 L ྛ࢙࢘ࣝ࡟ῧຍࡋ㸦PFA ᭱⤊⃰ᗘࡣ㸰%㸧
ࠊᐊ ࡛ 30 ศ㛫㟼⨨ࡍࡿࠋ⁐ゎཬࡧỿ㝆ฎ⌮㸸PFA ࢆ㝖ࡁࠊPBS ࡟ࡼࡿὙί㸦100 L ῧຍࠊ10 ศ㟼⨨ࠊPBS ࡢ㝖ཤ㸧ࢆ㸰ᅇ⾜ࡗࡓᚋࠊ50 L ࡢ Buffer QG ࢆྛ࢙࢘ࣝ࡟ῧຍࡋࠊ37Υ࡛㸯᫬㛫ᇵ㣴ࡍࡿࠋ௨ୖࡢฎ⌮࡟ࡼࡗ࡚ࠊᙧᡂࡉࢀࡓࢥࣟࢽ࣮ࡢ᰾࡜
࣑ࢺࢥࣥࢻࣜ࢔ࡀࡑࢀࡒࢀ㟷ࠊ㉥࡟ᰁⰍࡉࢀࠊࡉࡽ࡟ࢥࣟࢽ࣮ࡣ࢙࢘ࣝᗏ㒊࡟ỿ㝆ࡍࡿࠋ ⏬ീゎᯒࢆ⾜࠺࡜ࡁࡲ࡛ࠊࣉ࣮ࣞࢺࡣ㐽ගࡋ෭ⶶᗜ࡛ಖ⟶ࡋ࡚࠾ࡃ㸦ᇵᆅࡢ⵨Ⓨࢆ㜵ࡄࡓࡵࠊPBS ࢆྛ࢙࢘ࣝ࡟ῧຍࡋ࡚࠾ࡃ㸧ࠋ
2.3 ⏬ീࡢྲྀᚓ 㸲ಸࡢᑐ≀ࣞࣥࢬࢆ౑⏝ࡋࠊ96 ࢙࢘ࣝࣉ࣮ࣞࢺ㸯࢙࢘ࣝ㎶ࡾࠊ㸲ど㔝ࡢ⏬ീࢆྛ࢙࢘ࣝ
࡛ྲྀᚓࡍࡿࠋ㸱ࡘࡢࢳࣕࣥࢿࣝ㸦㟷ࠊ㉥ࠊ᫂ど㔝㸧࡛ࠊࡑࢀࡒࢀ࡛ྲྀᚓࡍࡿࠋ
2.4 ⏬ീゎᯒ 㸯࢙࢘ࣝ㎶ࡾ4ど㔝ࡢ⏬ീࡢࡘ࡞ࡂྜࢃࡏฎ⌮ࢆ⾜࠸ࠊ㸯࢙࢘ࣝ඲యࡢ⏬ീࢆ⏕ᡂࡋ࡚࠾ࡃࠋ࠶ࡽ࠿ࡌࡵタᐃࡋࡓゎᯒࢫࢡࣜࣉࢺࢆ⏝࠸㸦ホ౯ᣦᶆ㸸኱ࡁࡉࠊ┿෇ᗘࠊ⺯ගᙉᗘ㸧ࠊ㟷ཬࡧ㉥ࡢࡑࢀࡒࢀࡢ⺯ග⏬ീ࠿ࡽㄆ㆑ࡉࢀࡓ㡿ᇦࢆᢳฟࡋࠊࡑࢀࡽࡀ㔜࡞ࡾྜࡗࡓሙྜࠊࢥࣟࢽ࣮᭷ࡾ࡜ุᐃࡍࡿࠋࡲࡓࢹࣈࣜ➼ࡢ㠀≉␗ⓗ࡞ᰁⰍ࡛ࡣ࡞࠸ࡇ࡜࡞࡝ࢆ☜ㄆࡍࡿࡓࡵࠊ᫂ど㔝ീ࡛ࢥࣟࢽ࣮ࢆ┠どࡍࡿࠋ㸫㸫

2.5 㝧ᛶᑐ↷⣽⬊࡟࠾ࡅࡿ᳨ฟឤᗘࡢ☜ㄆ㸦107ಶࡢhMSC୰࡟ΰᅾࡍࡿ㸯ಶࡢHeLa⣽⬊ࡢ᳨ฟࡢሙྜ㸧
 HeLa⣽⬊ࡢㄪ〇㸸HeLa༢୍⣽⬊ࡣࠊ50~100ಶ/mlࡢHeLa⣽⬊ᠱ⃮ᾮࢆㄪ〇ࡋࠊ10 Lࡎࡘࢸࣛࢧ࢟ࣉ࣮ࣞࢺࡢྛ࢙࢘ࣝ࡟ศὀࡍࡿࠋ㢧ᚤ㙾ୗ࡛HeLa⣽⬊༢୍⣽⬊ࡀᏑᅾࡍࡿ࢙࢘ࣝ
ࢆ☜ㄆࡋ࡚࠾ࡃࠋhMSCࡢㄪ〇㸸hMSC 107ಶ࠿ࡽ࡞ࡿ⣽⬊ᠱ⃮ᾮࢆㄪ〇ࡋࠊࣜࢨ࣮ࣂ࣮ෆ
࡛1.2%࢔࣮࢞ࣟࢫ⁐ᾮࠊ20%FBSྵ᭷2×DMEMᇵᆅ࡜ΰࡐྜࢃࡏࡿ㸦౛㸸2.5 x 106ಶ/mLࡢ
hMSCᠱ⃮ᾮ4.4 mL㸩1.2%࢔࣮࢞ࣟࢫ⁐ᾮ4.4 mL㸩20% FBS ྵ᭷2 × DMEMᇵᆅ4.4 mL㸧ࠋࡉࡽ࡟ࠊࢸࣛࢧ࢟ࣉ࣮ࣞࢺୖࡼࡾࣆ࣌ࢵࢺ࡛༢㞳ࡋࡓHeLa༢୍⣽⬊ࢆΰධࡉࡏࠊ࣐ࣝࢳࢳ
ࣕࣥࢿࣝࣆ࣌ࢵࢺࢆ⏝࠸ࠊ160࢙࢘ࣝ㸦㸰ᯛࡢ96࢙࢘ࣝࣉ࣮ࣞࢺ࡟80࢙࢘ࣝࡎࡘ㸧࡟ศὀ
ࡍࡿࠋ75 Lࡢ⣽⬊/㌾ᐮኳᒙ୰࡟62,500ಶࡢMSC࡜0.00625ಶࡢHeLa⣽⬊ࡀྵࡲࢀࠊࡍ࡞ࢃ
ࡕ160࢙࢘ࣝ୰㸯࢙࢘ࣝ࡟㸯ಶࡢHeLa⣽⬊ࡀྵࡲࢀࡿࡇ࡜࡟࡞ࡿࠋ
 ๓㏙ࡢ᪉ἲ࡟ἢࡗ࡚ࠊ㌾ᐮኳᇵ㣴ཬࡧ⏬ീゎᯒࢆ⾜࠺ࠋࡲࡓࠊHeLa⣽⬊ࡀᮍΰධ࡛࠶ࡿ
hMSCࡢࡳ࡛ࡢᇵ㣴ࡶేࡏ࡚⾜࠺ࡇ࡜࡟ࡼࡾࠊ㝜ᛶᑐ↷࡜ࡋ࡚ࢥࣟࢽ࣮ࡀ඲ࡃ᳨ฟࡉࢀ࡞
࠸ࡇ࡜ࢆ☜ㄆࡍࡿࠋ
3. ṇᖖ⣽⬊୰ࡢᝏᛶᙧ㉁㌿᥮⣽⬊ΰᅾࡢ᭷↓ࡢホ౯ 㝧ᛶᑐ↷⣽⬊ࡢ⤖ᯝ࡟ᇶ࡙࠸࡚ࠊ㝧ᛶᑐ↷⣽⬊┦ᙜࡢᝏᛶᙧ㉁㌿᥮⣽⬊ࡢΰᅾࡢ᭷↓ࡢホ౯ࢆ⾜࠺ࠋHeLa ⣽⬊ࢆ㝧ᛶᑐ↷⣽⬊࡜ࡍࡿሙྜࠊHeLa ⣽⬊┦ᙜࡢ⣽⬊ࡢΰᅾࡢ᭷↓ࢆุᐃࡍࡿࡇ࡜࡟࡞ࡿࠋ㝧ᛶᑐ↷⣽⬊ࡢ⤖ᯝ࠿ࡽࠊヨᩱࢆศ⏬ࡋࡓ㸯࢙࢘ࣝ࡟࠾࠸࡚ࢥࣟࢽ࣮ࡀ
ᮍ᳨ฟ࡜࡞ࡿ☜⋡㸦㸻ࢥࣟࢽ࣮ࡀ࡞࠸࢙࢘ࣝᩘ㸭ศ⏬ᩘ㸦ࢥࣟࢽ࣮ࡀ࡞࠸࢙࢘ࣝᩘࡢ☜⋡ศᕸ㸧㸧ࡀᚓࡽࢀࡿࠋ㸯ᅇࡢヨ⾜㸦」ᩘ࢙࢘ࣝ࡬ࡢヨᩱࡢศ⏬㸧ࡢ඲࡚࡟࠾࠸࡚ࢥࣟࢽ࣮ࡀᮍ
᳨ฟ࡜࡞ࡿ☜⋡ x㸦=ヨᩱࢆศ⏬ࡋࡓ㸯࢙࢘ࣝ࡟࠾࠸࡚ࢥࣟࢽ࣮ࡀᮍ᳨ฟ࡜࡞ࡿ☜⋡^ศ⏬࢙࢘ࣝᩘ㸧ࡀᚓࡽࢀࡿࠋn ᅇࡢヨ⾜඲࡚࡟࠾࠸࡚ࢥࣟࢽ࣮ࡀᮍ᳨ฟ࡜࡞ࡿ☜⋡㸦ഇ㝜ᛶ⋡㸧yࡣࠊy = xn ࡜⾲ࡉࢀࠊn = log y / log x ࡜࠸࠺ᘧࡀᑟ࠿ࢀࡿࠋࡇࡢᘧࢆ⏝࠸࡚ࠊチᐜ࡛ࡁࡿഇ
㝜ᛶ⋡࡟ᛂࡌࡓヨ⾜ᅇᩘࢆ⟬ฟࡍࡿࡇ࡜ࡀྍ⬟࡛࠶ࡿࠋࡍ࡞ࢃࡕࠊヨ㦂⣽⬊ヨᩱ࡟࠾ࡅࡿᝏ
ᛶᙧ㉁㌿᥮⣽⬊ࡢΰᅾࡢྰᐃ࡟ᚲせ࡞ヨ⾜ᅇᩘࢆ㝧ᛶᑐ↷⣽⬊ࡢ⤖ᯝ࠿ࡽぢ✚ࡶࡿࡇ࡜ࡀ
ྍ⬟࡜࡞ࡿࠋ௨ୗ࡟౛ࢆ♧ࡍࠋ
 107 ಶࡢ hMSC ࡟㸯ಶࡢ HeLa ⣽⬊ࢆΰධࡉࡏࡓ⣽⬊ヨᩱࢆ㝧ᛶᑐ↷࡜ࡋࠊ௨ୗࡢ⾲࡟♧ࡍࡼ࠺࡞⤖ᯝࡀᚓࡽࢀ࡚࠸ࡿ࡜ࡍࡿࠋ
107 ಶࡢ hMSC ࡟㸯ಶࡢ HeLa ⣽⬊ࢆΰධࡉࡏࡓ⣽⬊ヨᩱࢆ 160 ࢙࢘ࣝ࡟ศ⏬ࡋࠊ㌾ᐮኳࢥࣟࢽ࣮ᙧᡂヨ㦂ࢆ⾜ࡗࡓ㸦ヨ⾜ᅇᩘ 6 ᅇ㸧

㸯࢙࢘ࣝ
ෆࡢࢥࣟ
ࢽ࣮ᩘ

࢙࢘ࣝᩘ
ヨ⾜㸯

ヨ⾜㸰

ヨ⾜㸱

ヨ⾜㸲

ヨ⾜㸳

ヨ⾜㸴

ᖹᆒ

ࡢ☜⋡ศ
ᕸ

0

159

160

159

159

160

159

159.3

0.9956

1

1

0

1

1

0

1

0.7

0.0044㸫㸫

 1 ࢙࢘ࣝ࡟࠾࠸࡚ࢥࣟࢽ࣮ࡀᮍ᳨ฟ࡜࡞ࡿ☜⋡ࠊࡍ࡞ࢃࡕࢥࣟࢽ࣮ࡀ࡞࠸࢙࢘ࣝᩘࡢ☜⋡ศᕸ㸦ࢥࣟࢽ࣮ࡀ࡞࠸࢙࢘ࣝᩘ㸭ศ⏬ᩘ㸻159.3㸭160㸧ࡣࠊ0.9956 ࡛࠶ࡿࠋ㸯ᅇࡢヨ⾜㸦」
ᩘ࢙࢘ࣝ࡬ࡢヨᩱࡢศ⏬㸻160㸧ࡢ඲࡚࡟࠾࠸࡚ࢥࣟࢽ࣮ࡀᮍ᳨ฟ࡜࡞ࡿ☜⋡ xࠊࡍ࡞ࢃࡕ
ヨᩱࢆศ⏬ࡋࡓ㸯࢙࢘ࣝ࡟࠾࠸࡚ࢥࣟࢽ࣮ࡀᮍ᳨ฟ࡜࡞ࡿ☜⋡ศ⏬࢙࢘ࣝᩘࡣࠊ0.9956160 =0.4938 ࡜ ࡞ ࡿ ࠋ ౛ ࠼ ࡤ ࠊ 1% ࡢ ☜ ⋡ ࡛ ഇ 㝜 ᛶ ࡀ ࠶ ࡿ ࡇ ࡜ ࢆ チ ᐜ ࡍ ࡿ ሙ ྜ ࠊ n =log(0.01)/log(0.4938) = 6.526 ࡜࠸࠺್ࡀᚓࡽࢀࡿࠋࡍ࡞ࢃࡕࠊ࠶ࡿ⣽⬊ヨᩱ୰࡟ HeLa ⣽⬊┦ᙜࡢᝏᛶᙧ㉁㌿᥮⣽⬊ࡀ 1/107 ࡢ๭ྜ࡛ΰᅾࡋ࡚࠸࡞࠸ࡇ࡜ࢆ♧ࡍ࡟ࡣࠊ㝧ᛶᑐ↷⣽⬊࡜ྠᵝࡢ᧯సࢆ㸵ᅇヨ⾜ࡋࠊࢥࣟࢽ࣮ࡀᮍ᳨ฟ࡛࠶ࡿࡇ࡜ࡀ☜ㄆ࡛ࡁࢀࡤࡼ࠸࡜⪃࠼ࡽࢀࡿࠋ

㸫㸫㸺ཧ⪃᝟ሗ 㸼ΰᅾࡍࡿᙧ㉁㌿᥮⣽⬊ࡢ᳨ฟἲ࡜ࡋ࡚ࡢ⣽⬊ቑṪ≉ᛶゎᯒฟ඾1㸸Kono K, Takada N et al. Characterization of the cell growth analysis for detection of immortal
cellular impurities in human mesenchymal stem cells. Biologicals. 2015:43:146-9. (See also: Kono K,
Takada N et al. Corrigendum to "Characterization of the cell growth analysis for detection of immortal
cellular impurities in human mesenchymal stem cells" [Biologicals 43 (2) (March 2015) 146-149].
Biologicals. )ฟ඾2㸸Hasebe-Takada N, Kono K et al. Application of cell growth analysis to the quality
assessment of human cell-processed therapeutic products as a testing method for immortalized
cellular impurities. Regen Ther. 2016;5:49-54. (A corrigendum is in press.)
࠙᪉ἲࠚ
1. ⣽⬊
 ࣄࢺ㦵㧊⏤᮶㛫ⴥ⣔ᖿ⣽⬊㸦hMSC㸧ࡣࠊ㸳⥅௦┠ࡲ࡛ࡣ Mesenchymal Stem Cell Growth
Medium㸦MSCGM㸧࡛ᇵ㣴ࡍࡿࠋࣄࢺ⬡⫫⏤᮶ᖿ⣽⬊㸦ADSC㸧ࡣࠊ㸳⥅௦┠ࡲ࡛ࡣ ADSCBulletKit ࡛ᇵ㣴ࡍࡿࠋHeLa ⣽⬊ࡣࠊEagle’s minimum essential medium ࡟ 10% ࢘ࢩ⫾ඣ⾑Ύ
㸦FBS㸧
ࠊ0.1 mM 㠀ᚲ㡲࢔࣑ࣀ㓟⁐ᾮࠊ50 U/mL ࣌ࢽࢩࣜࣥࠊ50 mg/mL ࢫࢺࣞࣉࢺ࣐࢖ࢩ
ࣥࢆຍ࠼ࡓᇵᆅ࡛ᇵ㣴ࡍࡿࠋhTERT ࡛୙Ṛ໬ࡋࡓ⬡⫫⏤᮶㛫ⴥ⣔ᖿ⣽⬊㸦ASC52telo㸧ࡣࠊ
ADSC-BulletKit ࡛ᇵ㣴ࡍࡿࠋ
2. ⣽⬊ቑṪ≉ᛶゎᯒ 㸳⥅௦┠ࡢ 1 × 106 ಶࡢ hMSC ࡟ࠊࡑࢀࡒࢀ 1 x 103 ಶ㸦0.1%)ࠊ1 x 102 ಶ㸦0.01%㸧ࠊ10 ಶ
㸦0.001%㸧ࠊ㸯ಶ㸦0.0001%㸧ࡢ HeLa ⣽⬊ࢆΰධࡉࡏࠊT175 ࣇࣛࢫࢥ࡟᧛✀ࡍࡿࠊཪࡣࠊ5⥅௦┠ࡢ 1 × 106 ಶࡢ ADSC ࡟ࠊࡑࢀࡒࢀ 1 x 103 ಶ㸦0.1%㸧
ࠊ1 x 102 ಶ㸦0.01%㸧
ࠊ10 ಶ㸦0.001%㸧
ࡢ HeLa ⣽⬊ࢆΰධࡉࡏࠊT175 ࣇࣛࢫࢥ࡟᧛✀ࡍࡿࠋ⣽⬊ࡣࠊDulbecco’s Modified Eagle’s
Medium 㸦DMEM㸧 ࡟ 10% FBSࠊ50 U/mL ࣌ࢽࢩࣜࣥࠊ50 mg/mL ࢫࢺࣞࣉࢺ࣐࢖ࢩࣥࢆ
ຍ࠼ࡓᇵᆅ 40 mL ࡛ᇵ㣴ࡋࠊ2~3 ᪥ẖ࡟ᇵᆅ஺᥮ࡍࡿࠋ࠾ࡼࡑ 90%ࢥࣥࣇ࢚ࣝࣥࢺ࡟㐩ࡋࡓ⣽⬊ࡣࠊࣜࣥ㓟⦆⾪⏕⌮㣗ሷỈ㸦PBS㸧࡛Ὑ࠸ࠊ0.05% ࢺࣜࣉࢩࣥ-EDTA ⁐ᾮ࡛ࣇࣛࢫࢥ
࠿ࡽ๤㞳ࡍࡿࠋ๤㞳ࡋࡓ⣽⬊ࡣࠊ450 × gࠊ5 ศ㛫㐲ᚰศ㞳ࡋࠊᇵᆅୖΎࢆ㝖࠸ࡓᚋࠊ᪂㩭ᇵᆅ࡛⣽⬊ࢆᠱ⃮ࡍࡿࠋᠱ⃮ࡋࡓ⣽⬊ࡢ୍㒊ࢆࠊࢺࣜࣃࣥࣈ࣮ࣝ⁐ᾮ࡛ᰁⰍࡋࠊ⮬ືࢭࣝ࢝࢘
ࣥࢱ࣮࡛⣽⬊ᩘࢆィ ࡍࡿࠋ1 × 106 ಶࡢ⣽⬊ࢆ T175 ࣇࣛࢫࢥ࡟᧛✀ࡋࠊḟࡢ⥅௦ࡲ࡛ᇵ㣴ࡍࡿࠋࡇࡢ୍㐃ࡢ᧯సࢆ 10 ⥅௦┠㸦HeLa ⣽⬊ࢆࢫࣃ࢖ࢡࡋࡓ hMSC㸧ཪࡣ 20 ⥅௦┠㸦ASC52telo ⣽⬊ࢆࢫࣃ࢖ࢡࡋࡓ ADSC㸧ࡲ࡛⧞ࡾ㏉ࡍࠋ⣽⬊ቑṪ㏿ᗘࡣୗグࡢᘧࢆ⏝࠸࡚⟬ฟࡍࡿࠋ
Rn = [log2(Nn+1 / Nn)]/(Dn+1 - Dn)
Nk N ⥅௦᫬ࡢ⣽⬊ᩘࠊ Dk N ⥅௦᫬ࡢ᪥ᩘ

㸫㸫 ୙Ṛ໬⣽⬊ΰᅾࡢุᐃࡣࠊ⣽⬊ቑṪ㏿ᗘࢆ㸳⥅௦┠࡜ẚ㍑ࡋࠊ᭷ព࡞ᕪࡢ᭷↓ุ࡛᩿ࡍࡿࠊ
ཪࡣࠊ㝜ᛶᑐ↷ࡢ⤒᫬ⓗ࡞⣽⬊ቑṪ㏿ᗘ࡜ẚ㍑ࡋุ࡚᩿ࡍࡿࠋ

㸫㸫