THIS PAGE MAY BE REMOVED BEFORE SUBMISSIONSTEERING COMMITTEE FOR THE UK STEM CELL BANK AND FOR
THE USE OF STEM CELL LINESAPPLICATION FORM TO IMPORT OR EXPORT HUMAN STEM CELL LINE(S)INTO OR OUT OF THE UNITED KINGDOM
Notes to Applicants(Please read these notes before completing the application form)·The absence of the required stem cell line(s) from the UK Stem Cell Bank catalogue should first be confirmed
by checking the UK Stem Cell Bank catalogue at http://www.ukstemcellbank.org.uk·It is important that this application is understandable by lay members and any abbreviations explained.

Submit your completed application form by email to the Secretary of the Stem Cell Steering Committee:
stemcellsecretary@headoffice.mrc.ac.uk
For general information contact:
The Secretary to the Steering Committee for the UK Stem Cell Bank and for the Use of Stem Cell Lines,
2nd Floor David Phillips Building
Polaris House
North Star Avenue
SwindonWiltshire SN2 1FL
Tel:+44 (0)20 7395 2247
For scientific information contact:
Dr Megan Dowie:or
UK Stem Cell Bank:

megan.dowie@mrc.ukri.org
enquiries@ukstemcellbank.org.uk

The following document must accompany all applications:·A one page CV for the Principal Investigator (Applicant)

The following documents must accompany any applications for stem cell lines for clinical use:···

A copy of ethics committee approval (or equivalent)
A copy of the information given to participants/patients in the clinical study/trial
A copy of the consent form given to participants

If submitting electronically, PDF files of WORD documents are acceptable. Paper copies may be submitted to theSecretary, but must be accompanied by a completed copy of the application form.
Key to abbreviations
HESC: Human Embryonic Stem Cell (line)
MHRA: Medicines and Healthcare products Regulatory Agency
NIH:National Institute of Health (USA)

HFEA: Human Fertilisation and Embryology Authority
HTA:
Human Tissue Authority
UKSC: UK Steering Committee

Notes to Sections
Note 1: List each cell line separately and use the cell line name designated by the originator.
Note 2: The type (embryonic, foetal, or adult), the Grade (either Research or Clinical) and the country where the cell line originated should beentered in the box provided of each stem cell line named.
Note 3: State whether each line is listed on either the US NIH (http://stemcells.nih.gov/research/registry/) or UKSC Register of Stem CellLines or neither.
Note 4: You must inform the UK Steering Committee if collaborators join the project subsequent to this application.
Note 5: The UK Steering Committee needs to satisfy itself that hESC lines are not used for trivial purposes and their uses are within the remit ofHFEA regulations. The Stem Cell Steering Committee will not conduct a scientific review of experimental detail or repeat the peer review.
Note 6: The Steering Committee considers all applications on a case by case basis and appreciates that in the area of consent that there may
be occasions when not all the criteria listed in Section 3 are fulfilled. The Steering Committee reserves the right to ask for original
documentation if considered necessary.
Note 7: The document The Code of Practice for the Use of Stem Cell Lines can be found on both the UK Stem Cell Bank and the Medical

Research Council websites

FOR OFFICE USE ONLYSCSC Application No. _____________________________APPLICATION FORM TO IMPORT/EXPORT A HUMAN STEM CELL LINE
INTO OR OUT OF THE UNITED KINGDOMSECTION 1General Information

Complete all boxes
1.1 Name and title of Principal Applicant:Masatsugu Ema

1.2 Title of Project (for which cell lines are requested):
Elucidation of cellular and molecular mechanism of early human development

1.3 Are you applying to:(Check only one box)

Export stem cell lines from the UK to a foreign country:
Import stem cell lines from a foreign country into the UK:☑

Import stem cell lines from the UK into a foreign country (overseas applicants):

1.5 Name and title of recipient (if exporting stem cell lines from the UK):

1.6 Name and title of provider (if importing stem cell lines):
Austin Smith, Professor, Director (Exeter University)
1.7 Name(s) of cellline(s) (see Note 1):

Type of cell line(s)(see Note 2):

Grade(see Note 2):

Country of origin(see Note 2):

Register
NIH / UKSC / none(see Note 3):

CAMe001-A (HNES1)

embryonicResearchUKUKSC

For HESC lines derived in the UK, please provide the HFEA licence number and HFEA centre number
Name of Cell Line:CAMe001-AHFEA Licence Number

HFEA Centre Number(under which cell line was derived):(for the centre from which the embryo was obtained):

R0178

0252

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FOR OFFICE USE ONLYSCSC Application No. _____________________________SECTION 2A

Applicant Details

2.1 Name and title of Principal Applicant:Post held:

Masatsugu Ema, Professor

2013

Address:

Telephone: 81- 77-548-2334

520-2192, Seta, Tsukinowa-cho, Otsu,Shiga, Japan

Fax: 81- 77-548-1990
E-mail: mema@belle.shiga-med.ac.jp(Complete only if different from 2.1 above):

2.2 Name and title of contact person

Post held:

Address:

Telephone:
Fax:
E-mail:SECTION 2B

Recipient Details(Complete only if different from 2.1 above)

2.3 Name and title of recipient:

Address:

Post held:

Telephone:
Fax:
E-mail:SECTION 2C

Provider Details(Complete only if different from 2.1 above)

2.4 Name and title of provider of the cell lines:

Post held:

Austin Smith, professor
Address:

Telephone: +44 (0) 1392 72 3042

Living Systems Institute, University of Exeter
Stocker Road, Exeter EX4 4QD, United Kingdom

Fax:
E-mail: austin.smith@exeter.ac.uk

SECTION 2DCollaborators

Provide names and institutions of all those collaborators who will have access to the stem cell line(s) listed
above as part of this application (see Note 4)
2.5 Name(s) and title(s) of collaborator(s)Institution(s)Masatsugu Ema, professor
Shoma Matsumoto, Assistant professor
Masanaga Muto, Assistant professor
Eiichi Okamura, Assistant professor

Shiga University of Medical Science
Shiga University of Medical Science
Shiga University of Medical Science
Shiga University of Medical Science

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FOR OFFICE USE ONLYSCSC Application No. _____________________________

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FOR OFFICE USE ONLYSCSC Application No. _____________________________SECTION 3A

Details of Research Project(for which stem cell lines are being requested)

3.1 Title of Research Project:
Elucidation of cellular and molecular mechanism of early human development

3.2 Abstract of Research Project including aims and objectives. (See note 5)(Approx 300 words):
Our aim is to elucidate the cellular and genetic mechanism of early human development. Although my laboratory
has been studying about the early development of Cynomolgus monkey, a nonhuman primate, as an animal modelto understand early human development and found that there are some primate-specific mechanisms underlying
early cell lineage specification, there is still evolutionary distance between monkey and human. To understand theearly human development, we are planning to generate human blastoid from HNES1, a human naïve ES cellline according to the previous reports (Yanagida et al., 2021, doi: 10.1016/j.stem.2021.04.031; Kagawa et al., 2021
doi: 10.1038/s41586-018-0051-0) and to analyze the gene expression and epigenetic state at single cell level andobserve cellular dynamics under microscope. Stem cells representing epiblast, trophectoderm and primitive
endoderm are re-derived from the human blastoid. Since the generation efficiency of the blastoid is not optimal, we
are improving the ES cells by modulating gene functions with genome editing, small chemicals and antibodies.
After the blastoid are sufficiently characterized, the ES cells are subjected to co-culture with endometrialorganoids to evaluate the capability of interaction with endometrial cells and initial process of placentation.
Endogenous gene functions are modulated by genome editing technique, neutralizing antibody and small
chemicals, and then the ES cells with modified gene function are tested for the capability to blastoid formation andthe embryo-endometrial interaction.
During the above culture, we follow the 14 day rule. We observe the blastoid every days by microscopic
observation and stop culturing before the sign of gastrulation. We do not transplant them into uterus of animal.

3.3 Have you previously received approval from the UK Steering Committee to use stem cells for aresearch project?
YesNo ☑

YesNo ☑

If Yes give UK Stem Cell Steering Committee (SCSC) number

3.4 Has the research project been subjected to peer review?

If Yes provide details (Funding body etc)

If No please explain why this is the case (e.g. generation of preliminary data), state how the research will besupported
I have submitted the application forms, but not obtained the approval yet. I also have submitted severalfunding. In the meanwhile, in-house funding in our University supports this study.

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FOR OFFICE USE ONLYSCSC Application No. _____________________________SECTION 3A (continued)
3.5 Does the research project include experiments in animals, excluding teratoma assays in smallmammals?
Yes

No ☑

If Yes provide details:

3.6 Do you intend to perform experiments creating hES cell/animal embryo aggregation chimaeras?
YesNo ☑

If Yes provide details:

3.7 Are all experiments involving animals covered by appropriate Home Office Animal Procedures
Licences (or their equivalent if the cell line is to be used outside of the UK)?
Yes

No ☑

3.8 Do you intend to use the stem cell lines in clinical trials / therapy
Yes

No ☑

SECTION 3B (to be completed only if Clinical Grade stem cell lines have been requested)
3.8 Has the stem cell line(s) been derived in facilities accredited / licensed by an equivalent of the UK
MHRA or HTA
Yes

No

3.9 Do you have access to facilities accredited by the MHRA, or the HTA (or their equivalent where theapplication is from overseas)
YesNoIf Yes provide details (e.g. regulations/directives under which the facilities are accredited)

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FOR OFFICE USE ONLYSCSC Application No. _____________________________SECTION 4Consent

YOU NEED ONLY COMPLETE THIS SECTION IF THE STEM CELLS IN THIS APPLICATION:·are somatic stem cell lines derived from foetal or adult tissue, OR are of embryonic origin andwere derived outside the UK;·are not listed on either the Register of Steering Committee Approved Stem Cell Lines or the NIHRegistry.

ANDComplete ALL boxes in this section (see note 6).
4.1 Was the study for deriving the cell lines(s) named in this application approved by an ethics
committee (or equivalent if application is from outside the UK):
Yes

NoThe following criteria constitute best practice in the UK for informed consent.
4.2 Have you confirmed with the originator that at the time of consenting, the donor(s) was informed:
i about the specific research project, including any tests that may be performed as part of the licensed
research
project on embryos or cells derived from the embryos
Yes

Noii that any stem cell lines created may continue indefinitely and may be used in many different research
projects
Yes
iii that the decision whether to donate would not affect their treatment in any way
Yes

No
No

iv about whether the embryos/cells would be reversibly or irreversibly anonymised and the implications of thisYes

No

Yes

Nov whether any information will be fed back to the donor(s)vi that the donors may vary or withdraw their consent until the point the embryos/cells are used in the project
Yes

Novii that once the embryo/cells has been used in the project, the donor(s) have no control over any use of thecells or any stem cell lines derived
Yes

Noviii that stem cell lines derived in this project will be deposited in the UK Stem Cell Bank and the implications of
this including long term storage and use in other research projects and potential therapeutic applications
Yes

Noix that stem cell lines may not be generated where the consent places a constraint on future use
Yes

Nox that cell lines may be used for commercial purposes, but that donor(s) will not benefit financially from thisYes

Noxi that cell lines derived or discoveries made from them may be patented but donor(s) will not financiallybenefit
Yes

Noxii regarding how the research was funded, including any benefit which may accrue to researchers and/or their
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FOR OFFICE USE ONLYSCSC Application No. _____________________________

departments/companies
Yes

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No

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FOR OFFICE USE ONLYSCSC Application No. _____________________________SECTION 5Declaration

By submitting this application to the secretary to the Stem Cell Steering Committee, I confirm that:i. The information in this form is accurate to the best of my knowledge and belief and I take full
responsibility for it.
ii. I have read and understood the Code of Practice for the Use of Human Stem Cell Lines and agree toabide by this Code (see Note 7).
iii. The cell line(s) will only be used for the purposes set out in this application.
iv. The cell lines will only be used for:a. Research that is consistent with UK legislation (as specified in the Code of Practice for theUse of Stem Cell Lines and the recipient hereby agrees to abide by this Code.
b. Research which has the long term goal of helping to increase knowledge about serious
diseases and their treatment.
c. Basic cell research which underpins these aims.
d. Development of cell based therapies for clinical trials in respect of serious human diseases.
v. The cell lines will only be used for research that does not contravene UK legislation such as thatpertaining to reproductive cloning.
vi. The cells will only be used for research that is consistent with and does not contravene legislationin the country in which the recipient is working.
Signed on behalf on Host Institution

Signed by Principal Applicant(Person responsible e.g. Head of Department/Dean)(on behalf of all principal collaborators)

Date:

Date: February 20, 2022
Signed by Recipient(if the stem cell line(s)s are being exported from the UK to a foreigncountry)

Date: February 20, 2022
Name and title of Signatory for Host Institution:
Shinji Uemoto, President
Post Held

Institution

Postal Address:

Shiga University of Medical Science
Telephone: 81-77-548-2082

520-2192, Seta, Tsukinowa-cho, Otsu,Shiga, Japan

Fax: 81-77-548-2086
E-mail: hqsangaku@belle.shiga-med.ac.jp

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FOR OFFICE USE ONLYSCSC Application No. _____________________________FOR OFFICE USE ONLY
Date application received:
1. Principal Investigator’s CV received:

Yes

No

2. Recipients CV received

Yes

No

3. Copy of ethics committee approval received:

YesNo(clinical grade cells only)

4. Patient/participant information sheet received:(clinical grade cells only)

5. Copy of consent form received:(clinical grade cells only)

Not Applicable(if cells are ResearchGrade)

Yes

No

Not Applicable(if cells are ResearchGrade)

Yes

No

(if No complete 5 below)
Grade)

Not Applicable(if cells are Research

6. Record details of method used to ascertain that appropriate consent would be obtained from thepatients/participants.

Print Name:

Signature:

Date application considered by SC:
Date application approved:

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