REVIEW
Adipose-derived stem/progenitor cells: roles inadipose tissue remodeling and potential use for soft
tissue augmentation
Many features of adipose tissue-speciﬁc stem/progenitor cells, such as physiological function andlocalization, have recently been examined. Adipose-tissue turnover is very slow and its perivascularprogenitor cells differentiate into adipocytes in the next generation. The progenitor cells play importantroles in physiological turnover, hyperplasia and atrophy of adipose tissue, as well as in incidental remodeling,such as postinjury repair. Adipose tissue has been used as an autologous ﬁller for soft tissue defects,
despite unpredictable clinical results and a low rate of graft survival, which may be due to the relativedeﬁciency of progenitor cells in graft materials. A novel transplantation strategy, termed cell-assisted
lipotransfer, involves the enrichment of adipose progenitor cells in grafts; preliminary results suggest thisapproach to be safe and effective.
KEYWORDS: adipocyte  adipose-derived stromal cells  angiogenesis  breast
augmentation  endothelial progenitor cells  ﬁbrosis  HGF  pericytes stromal vascular fraction

Kotaro Yoshimura†,
Hirotaka Suga
& Hitomi Eto†

Adipose tissue has been considered an organ ofenergy storage, an endocrine organ, a soft tissue
ﬁller (augmentation by micro-fat grafting) anda cosmetically unnecessary tissue discarded byliposuction. It is now also regarded as a promising source of adult stem cells, as adipose tissue
has plenty of progenitor cells, some of which candifferentiate into diverse lineages [1] . A component of ﬁbroblast-like stromal cells obtained
from liposuction aspirates can differentiate into
various cell lineages [1] , including adipogenic,
osteogenic [2] , chondrogenic [3] , myogenic [4] ,cardiomyogenic [5] and neurogenic [6] . Thus, adipose tissue-derived stromal cells are now called
adipose-derived stem/stromal/progenitor cells(ASCs) and are expected to become a valuable
tool for a wide range of cell-based therapies [7] .
ASCs are believed to act as progenitors of adipocytes and vascular cells [8] , reside between adipocytes, around vessels or in the extracellularmatrix, and contribute to the turnover of adipose
tissue [9] . Adipose-tissue turnover is known to bevery slow in humans (2–10 years) [9,10] . Human
ASCs are distinct from other mesenchymal progenitors in their surface marker expression proﬁle; notably, ASCs express stem cell-associatedmarker CD34 in higher percentages than bonemarrow-derived mesenchymal stem cells anddermal ﬁbroblasts [11] .
A huge body of basic and translational
research using ASCs has been conducted andASCs are currently being used in some clinical trials, including treatments for bone defects(autologous fresh ASCs) [12] , rectovaginal ﬁstula(autologous cultured ASCs) [13] , graft-versushost disease (nonautologous ASCs) [14] and soft
tissue augmentation by progenitor-enriched fat
tissue grafting (autologous fresh ASCs) [15–18] .
ASCs have been found to have potential similarities to bone marrow-derived mesenchymal stem
cells and are now of great interest as a tool forcell therapies.

10.2217/17460751.4.2.265 © 2009 Future Medicine Ltd

Regen. Med. (2009) 4(2), 265–273

Author for correspondence:ĞƉĂƌƚŵĞŶƚŽĨWůĂƐƟĐ^ƵƌŐĞƌǇ͕hŶŝǀĞƌƐŝƚǇŽĨdŽŬǇŽ^ĐŚŽŽůŽĨDĞĚŝĐŝŶĞ͕ϳͲϯͲϭ,ŽŶŐŽ͕ƵŶŬǇŽͲŬƵ͕dŽŬǇŽϭϭϯͲϴϲϱϱ͕Japan
dĞů͗͘нϴϭϯϱϴϬϬϴϵϰϴ͖&Ăǆ͗нϴϭϯϱϴϬϬϴϵϰϳ͖ͲŵĂŝů͗ǇŽƐŚŝŵƵƌĂͲƉůĂΛŚ͘ƵͲƚŽŬǇŽ͘ĂĐ͘ũƉAdipose tissue & its
cellular components
Adipose tissue consists predominantly of adipocytes, ASCs, vascular endothelial cells, pericytes, ﬁbroblasts, macrophages and extracellular matrix [11] . Adipocytes constitute more than
90% of tissue volume owing to their large size
(50–130 μm diameter), yet the number of adipocytes is estimated to be less than 50% [19,20] .
Our recent survey, from whole-mount stainingof living adipose tissue, suggested the adipocyte
percentage is less than 30%. Adipose tissue isknown to be rich in microvasculature [21] andevery adipocyte has contact with capillaries [22] ,although the capillaries are a substantial distance from each other owing to the large cellsize of adipocytes.
Since the discovery of leptin, adipose tissue has been recognized as the largest endocrine organ. In addition to fatty acids, multiple factors such as leptin and adiponectin are
released from adipose tissue [20] . It has beenshown that most inf lammatory adipokines
ISSN 1746-0751

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REVIEW Yoshimura, Suga & Eto
10-year lifespan
Cell

ECM

Apoptosis
Apoptosis

Apoptosis

Apoptosis
ECM

Degradation

Function

Vasculature
Adipocyte

Function

Adipocyte
Release

D

re
iffe

ntia

tion

Enzyme(e.g., MMP)

Dif
fere
ntia
tion

ECM
ECM
ECM

Proliferation
Proliferation

Transient amplifying cells
Niche (va
scula
rw

all)

Stem progenitor cells
Regen. Med. © Future Science Group (2009)

Figure 1. Adipose-tissue turnover. It was recently revealed that adipose-tissue turnover is slow [9] and adipocyte progenitor cells areresident in the vasculature [42] . The ECM also renews itself. The average adipocyte lifespan is approximately 10 years [9] . Adipocytes andcapillaries may be derived from common progenitor cells [8] .
ECM: Extracellular matrix; MMP: Matrix metalloproteinase.

are released predominantly from cells otherthan adipocytes, such as ASCs and resident
macrophages [20] .
Stromal vascular fraction
Through collagenase digestion, a heterogeneous
cell mixture containing all cell types, except adipocytes, can be extracted from adipose tissue (orliposuction aspirates) as a cell pellet. Adipocytes
are disrupted into oil during the process and discarded as ﬂoating tissue and oil after centrifugation. The sedimented cell fraction is called thestromal vascular fraction (SVF) and is basicallystromal cells along with vascular endothelial andmural cells. The SVF also contains a substantial
number of circulating blood-derived cells suchas leucocytes and erythrocytes, although mostof the contaminated erythrocytes can be disrupted with hypotonic solution processing. Our
study identiﬁed freshly isolated ASCs as CD31CD34 + CD45-CD90 + CD105-CD146 - cells, butthey become CD105 + when plated [11] . Nucleate
266

Regen. Med. (2009) 4(2)cells contained in the SVF obtained fromlipoaspirates are composed of 37% leucocytes(CD45 +), 35% ASCs (CD31- CD34 + CD45 -),15% endothelial cells (CD31+ CD34 + CD45 -)and other cells (CD31-CD34-CD45-), although
the percentage of blood-derived cells strongly
depends on individual hemorrhage volume [19] .
ASCs can be extracted from both the ﬂoating
fatty portion and ﬂuid portion of liposuction
aspirates; however, the ﬂuid portion contains
much fewer adipose-derived cells and many
more blood-derived cells. In mice, the adipocyte
progenitor subpopulation was recently identiﬁed
as Lin-Sca1+ CD24 + CD29 + CD34 + cells [23] .
ASCs can be used clinically without cell
expansion if harvested from a large volume of
lipoaspirates because a sufﬁcient number of cells
can be obtained; 0.1–1 billion nucleate cells canbe obtained from 200 ml of aspirated fat tissue
and at least 10% of these cells are ASCs. The
use of freshly isolated cells likely leads to higher
safety and efﬁcacy in treatments compared with
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Adipose-derived stem/progenitor cells

cells expanded by culture; the US FDA (21 CFR
Parts 16, 1270 and 1271) regards cells cultured
even overnight as more-than-minimally manipulated cells, and cultured ASCs are known toshow a distinct phenotype to fresh ASCs [11,24] .
Some ongoing clinical trials employ freshly
isolated SVF, rather than puriﬁed or cultured
ASCs. As the SVF contains other cells, such as
vascular endothelial cells or macrophages, synergistic effects may be expected, as suggested bymany studies [25–28] .
ASCs in adipose tissue remodelingASCs have been shown to have angiogenic characteristics, to release angiogenic factors underischemia [29,30] or stimulation of growth factors [31] , and to experimentally differentiate into
vascular endothelial cells [2,32–35] . Thus, ASCs are
now considered to be bipotent progenitor cells forboth adipocytes and vascular cells, although thedifferentiation into vascular endothelial cells was
not frequently detected in in vivo studies [28,36]
and a standard in vitro protocol for endothelial
differentiation is not yet established. ASCs arethought to localize between adipocytes (co-localize
with capillaries), in the vessel walls or in the connective tissue; most of them show perivascular
localization. Some studies suggest the existence ofa cell population localized in the vascular wall thatcan differentiate into vessels [37,38] , while otherstudies indicate a possible identity between ASCsand vascular pericytes [39–42] . In addition, ASCs
have been shown to be incorporated into microvascular remodeling and exhibit a perivascular
phenotype [40] . Recently, it was discovered inmice that adipocyte progenitor cells are present
in adipose vasculature as mural cells [42] .
ASCs contribute to adipose-tissue turnover andprovide cells in the next generation (FIGURE 1) [9] .
Adipocytes have a lifespan of 2–10 years and are
replaced with next-generation cells derived from
ASCs after apoptosis [9,10] . ASCs are thought
to be the main proliferating cell population in
adipose-tissue remodeling, such as the repair
process after ischemia–reperfusion injury [31] , orin adipose tissue expansion induced by external
forces [Kato H et al., Unpublished Data] . Adipose tissue grows in adolescence or obesity and atrophieswith age or after tissue injury. These remodeling processes are thought to be in balance withadipocyte (either physiological or incidental)
apoptosis/necrosis and adipogenesis managed
by ASCs; these degenerative and regenerativechanges are always accompanied by capillary
remodeling (FIGURE 2) . Adipose-tissue atrophy
with age is likely due to a decrease in ASCs andfuture science group

REVIEWsubsequent impaired replacement in the next
generation, as is commonly seen in other tissues
and organs [43] .
Adipose tissue grafting forsoft tissue augmentation
Soft tissue augmentation is performed by grafting
autologous tissues or artiﬁcial materials to correct
inborn or acquired tissue defects, such as breastreconstruction, or for purely cosmetic purposes,
such as breast augmentation. Although it is nota life-saving procedure, the demand is huge; theincidence of breast cancer is increasing with one
in eight women now suffering from this disease inwestern countries [101] . Breast augmentation is themost frequently performed cosmetic surgery [102] ,carried out more than 300,000-times annuallyin the USA. Autologous fat transplantation is apromising treatment for soft tissue augmentation
because there is no associated incisional scarring or complications because of foreign materials. Although many innovative efforts to reﬁne

GrowthTissue turnoverPhysiological tissue cycle(an adipocyte dies every 4 s
per 1 cm3 adipose tissue)

Expansion,
hyperplasia

Developmental growth, obesity,
tissue expansion and lipoma

Atrophy

Aging, ischemia without recovery
and stem cell deficiency

Incidental
remodeling

Tissue repair after any injury,
ischemia–reperfusion andadipose grafting

Apoptosis

GrowthApoptosis

GrowthApoptosis
GrowthNecrosis,
apoptosis

Regen. Med. © Future Science Group (2009)

Figure 2. Balance between cell division and death in adipose tissue.
Adipose-tissue turnover is the physiological balance between cell growth andapoptosis. In hyperplasia (not hypertrophy), adipocyte progenitor cells divide more
frequently than adipocytes undergo apoptosis. In response to a decrease inprogenitor cells with age, tissue turnover results in atrophy. Adipose tissue
remodeling responds to various types of stimuli; degenerative and regenerative
events depend on the type and extent of stimuli. In all of the processes in theﬁgure, adipose tissue progenitor cells are involved in growth, replacement andrepair processes.

www.futuremedicine.com

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REVIEW Yoshimura, Suga & Eto
ECM
Dying cells

Recipient tissue injury by injectionof nonvascularized adipose tissue
Hypoxia
Hypoglycemia

ReleaseNecrosis
Apoptosis

bFGF

Bleeding
Platelet activation
ReleasePDGF, EGF,
TGF-β

IL-1, -6, -8
HGF

Adipose tissue andcapillary remodeling

ReleaseInflammatory cells

Adipogenesis, angiogenesis
inhibits fibrogenesis
Regen. Med. © Future Science Group (2009)

Figure 3. Cellular and molecular events after adipose tissue grafting. Adipose grafting induces
injury in the recipient tissue; bleeding from the host tissue activates platelets and various soluble
factors derived from platelets are released. At the same time, bFGF is released from injured tissue orcells and stimulates adipose-derived progenitor cells to release HGF, which promotes angiogenesis andinhibits ﬁbrogenesis [31] . Tissue injury further induces inﬂammatory cell inﬁltration and the release of
inﬂammatory cytokines. Transplanted adipose tissue is temporarily placed under ischemia and part of
the tissue survives after establishing vascularization. In the ischemia–reperfusion process, necrotizing
and repairing processes occur and adipose progenitor cells play key roles in adipose-tissue remodeling.
bFGF: Basic FGF; ECM: Extracellular matrix.

autologous lipoinjection have been reported,
problems such as unpredictability and a low rateof graft survival due to partial necrosis remain.
Implantation of artiﬁcial prostheses has been thestandard method of breast augmentation, withlipoinjection used by a limited number of plastic
surgeons [44] . The use of fat tissue in breasts has
been controversial owing to the lack of consensus on its safety and appropriateness because of
microcalciﬁcations that may cause confusion in
the evaluation of mammograms. However, autologous fat injection was recently re-evaluated asa potential alternative to artiﬁcial implants forbreast augmentation [15,17,18,44,45] , reﬂecting recent
advances in autologous fat transfer techniques
and the radiological detection of breast cancer.
It has not been well documented how adipose
grafts survive after lipoinjection. With lipoinjection, the recipient tissue is injured and bleeding
occurs. The grafted nonvascuralized adipose tissue
is placed under ischemia (hypoxia) and is temporarily nourished by diffusion from the surrounding host tissue for a few days until direct capillaryattachment is formed (FIGURE 3) . In response to
injury, tissue-bound basic FGF is released fromthe injured host tissue, especially from the extracellular matrix and dying cells [46] . Other factors
such as PDGF, EGF and TGF-E are released from
activated platelets in response to local bleeding [47] .
268

Regen. Med. (2009) 4(2)Inﬂammatory cells such as macrophages andlymphocytes are inﬁltrated and inﬂammatory
cytokines such as interleukins are secreted. During
the repairing process, adipocytes, known to be very
sensitive to hypoxia, are likely to die within 24 h
if the oxygen pressure is lower than its threshold.
ASCs, however, are thought to be more resistant
to ischemia as is the case for bone marrow-derived
mesenchymal stem cells, which can be functionalfor 72 h under ischemia [48] . In animal models forischemia–reperfusion injury of adipose tissue [31] ,ASCs were involved in the repair process after fat
grafting and played key roles in adipogenesis andangiogenesis. A preliminary study suggested evensurviving adipocytes die within a few months
after transplantation and are replaced with nextgeneration cells, possibly owing to the stress of
temporary ischemia. Therefore, the number offunctional ASCs is likely to be important for
tissue repair and remodeling.
Aspirated & intact fat tissue
Aspirated fat tissue, but not excised (intact) fat
tissue, can be used as lipoinjection material. Skin
incision is necessary to harvest excised fat tissue,
which is not acceptable for cosmetic purposes.
When aspirated, the fragile parts of adipose tissue are removed with negative pressure througha small suction cannula while honeycomb-likefuture science group

Adipose-derived stem/progenitor cells

ﬁbrous structures (connective tissues, vasculatures and nerves) remain in aspirated fatty layers.
We have found many adipocytes and capillaries
are ruptured and a larger number of dead cells
are contained in aspirated fat tissue. In addition,
aspirated fat tissue contains only half of the ASCs
compared with intact fat tissue (FIGURE 4) [35] . This
relative deﬁciency of ASCs in aspirated fat tissue
may be because a substantial portion of ASCs
are located around large vessels (within tunica
adventitia) and left in the donor tissue; andsome ASCs are released into the ﬂuid portion ofliposuction aspirates [11] . Large-sized vessels are

REVIEWlocated in the ﬁbrous part of the tissue, present inintact but not aspirated fat tissue. Thus, aspirated
fat tissue is regarded as relatively progenitor poor
as compared with intact fat tissue [35] .
Supplementation of adipose
progenitor cells in micro-fat grafting(cell-assisted lipotransfer)
As discussed earlier, aspirated fat tissue has asigniﬁcantly lower progenitor/mature cell ratio.
This low ASC/adipocyte ratio may be the main
reason for long-term atrophy of transplanted
adipose tissue, because ASCs are supposed to

Aspirated adipose

Excised adipose

JI

100 μm
100 μmFigure 4. Comparison of human aspirated and excised (intact) fat tissue obtained from a single site from one patient.
Macroscopic views (A & E), schematic (C & G) and electromicroscopic views (B, D, F & H; red scale bars = 200 μm, white scale bars =40 μm), and whole mount staining images (I & J; scale bars = 100 μm). The basic structure of adipose tissue was preserved in theaspirated fat, while some adipocytes and capillaries were disrupted. Vascular vessels, especially those of large size, were notably less inaspirated fat tissue compared with the excised fat tissue. Adipose-derived stromal cell yield from aspirated fat tissue was considerably less
(56 ± 12%) than that from excised fat tissue. B, D, F and H taken from [35] .

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REVIEW Yoshimura, Suga & Eto
Aspirated fat tissue(progenitor-poor fat)

Aspirated fat tissue(progenitor-enriched fat)Freshly isolated SVF

Erythrocytes(hypotonic
processing)

Others

Leukocytes

ASCs

Endothelial cells+

Regen. Med. © Future Science Group (2009)

Figure 5. Concept of cell-assisted lipotransfer. Relatively progenitor-poor aspirated fat tissue isconverted to progenitor-enriched fat tissue by supplementation with the SVF, which can be obtained
from adipose and ﬂuid portions of liposuction aspirates through collagenase digestion. SVF cells areattached to the aspirated fat tissue, which acts a scaffold in this strategy. The SVF contains 10–40%
of ASCs (CD34 + CD31- CD45 -), some of which have multipotency and can differentiate into several
lineages in vitro. The SVF also contains blood-derived cells (CD45 + cells) such as leukocytes.
ASC: Adipose-derived stromal cell; SVF: Stromal vascular fraction.

contribute to adipose tissue turnover by replacing adipocytes lost in the atrophying processwith next-generation adipocytes. There areat least three experimental studies, including
ours [35,49,50] , demonstrating that supplementationof adipose progenitor cells enhances the volume
or weight of surviving adipose tissue. Enrichmentof adipose progenitor cells by supplementation
with the SVF improves the progenitor/adipocyte
ratio; progenitor-poor aspirated fat tissue is converted to progenitor-rich tissue. In cell-assisted
lipotransfer (CAL) [15–18,35] , a novel approach toautologous fat transplantation, freshly isolated
SVF cells containing ASCs are attached to theaspirated fat, with the fat tissue acting as a living
bioscaffold before transplantation (FIGURE 5) .
There are four possible roles for ASCs in
CAL treatment, which were partly conﬁrmed
in preclinical studies [35,49,50] . First, ASCs candifferentiate into adipocytes and contribute toregeneration of adipose tissue. Second, ASCs
can differentiate into vascular endothelial cells
and also probably into vascular mural cells [2,32–
35,37] , resulting in the promotion of angiogenesis
and graft survival. Third, ASCs are known torelease angiogenic growth factors such as HGF
and SDF-1 in response to injury, hypoxia andother conditions [28–31,36] , and these factors inﬂuence surrounding host tissue. The ﬁnal, possibly most inﬂuential role, is that ASCs survive as
original ASCs [35] . As mentioned earlier, ASCs
reside between adipocytes or in the extracellular
270

Regen. Med. (2009) 4(2)matrix, especially around vessels, and contributeto the turnover of adipose tissue, which is known
to be very slow (2–10 years) [9,10] . However,surviving adipose grafts probably turnover
within the ﬁrst 2–3 months after transplantation, as suggested by adipose-tissue remodelingafter ischemia–reperfusion injury [31] and otherunpublished data. The grafts experience temporary ischemia followed by reperfusion injury;
therefore, the number of ASCs may affect the
replacement process and postoperative atrophy ofgrafted fat, which is known to commonly occur
during the ﬁrst 6 months after lipoinjection.
Clinical trials using cell-assisted
lipotransfer for soft tissue
augmentation, including
breast enhancement
As a potential alternative to artiﬁcial implants
for soft tissue augmentation, including breast
enhancement, we started a clinical trial of CAL in
2003. Preliminary results are reported elsewhere[15–18] . Currently, 307 patients (303 females andfour males) have undergone CAL; on the breastin 269 patients (including 177 cosmetic breast
augmentations, 52 breast implant replacements
and 40 postmastectomy breast reconstructions),
on the face in 48 patients (including three lupus
erythematosus profundus, two Romberg’s disease
and one scleroderma), on the hip in four patients,and on the hand in three patients (CAL was
performed at multiple sites in 15 patients).
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Adipose-derived stem/progenitor cells

Preliminary clinical results are generally satisfactory in terms of the natural texture, softness, and contour resulting from the soft tissue
augmentation and an absence of foreign materials. 3D measurements (Sppd-3E, Kiisya Co.
Ltd., Tokyo, Japan) that enabled volumetricevaluation of the breast mound with the patientin a standing position showed that graft takeranged from approximately 40 to 80% [17,18] .
Surviving fat volume varies substantially among
patients, and multiple factors are likely to affectthe clinical results; patient factors include skinredundancy of the breast and technical factors
include devices, graft fat preparation and injection techniques. Possible complications included
cyst formation and calciﬁcation derived from fat
necrosis, mainly due to inappropriate tissue preparation and injection technique. CT scans and
MRI showed that transplanted fat tissue survives
well and forms a considerably thick fatty layer
subcutaneously on and around the mammary
glands, and also between the mammary glands

REVIEWand the pectoralis muscles. ASC supplementation dramatically improves the ASC/adipocyte
ratio and is suggested to minimize adipose atrophy after transplantation, although further studies such as a blinded and controlled comparisonof CAL and traditional fat grafting are needed
to elucidate the effects of ASC supplementation(i.e., conversion to ‘progenitor-rich tissue’).
In the clinical trial, ectopic ﬁbrogenesis wasobserved in two patients injected with SVF
cells as a cell suspension separately from fat
grafts [51] . In cell-based therapies using adherent
mesenchymal stem cells, unfavorable behaviors
such as differentiation into myoﬁbroblasts havebeen reported [52,53] . This possibility of unexpected behaviors should be taken into accounteven if cells are derived from adult tissue andhave not been substantially manipulated. A
solution may be to adhere adipose-derived
adherent stem/progenitor cells to cells, tissue, extracellular matrix or biological scaffold
before administration.

Executive summary
 It was recently revealed that adipose-tissue turnover is very slow (2–10 years) and adipocyte
progenitor cells are present in the vasculature of adipose tissue. Recent studies have suggested theidentity of the progenitor cells and vascular pericytes.
 Adipose tissue contains a substantial amount (greater than adipocytes in number) of stromal cells,
termed adipose-derived stromal cells (ASCs). Some ASCs are multipotent and can differentiate into
various lineages.
Adipose tissue & its cellular components
 The stromal vascular fraction is the heterogeneous cell population obtained from collagenase
digestion of adipose tissue. It contains ASCs and vascular endothelial cells, as well as blood-derived
cell populations.
Adipose-derived stem/progenitor cells in adipose tissue remodeling ASCs divide, migrate and differentiate into adipocytes or vascular cells during the turnover or
remodeling process that adipose tissue undergoes to compensate for apoptotic or degenerativechanges. Every adipocyte needs direct contact with a capillary, thus adipogenesis is always
accompanied by capillary angiogenesis.
Adipose tissue grafting for soft tissue augmentation
 Micro-fat grafting is a promising method of soft tissue augmentation owing to theabsence of both foreign materials and conspicuous scarring. There are still some issues
to be resolved, including unpredictable effectiveness and long-term atrophy of grafted
fat tissue.
Aspirated & intact fat tissue Aspirated fat tissue, the material used in micro-fat grafting, has fewer adipose progenitor cells thanintact fat tissue. This may impair remodeling of the grafted tissue and lead to long-term atrophyof the grafts.
Supplementation of adipose progenitor cells in micro-fat grafting(cell-assisted lipotransfer) Preliminary results from our clinical trials using progenitor-enriched fat tissue grafting suggested
supplementation with stromal vascular fractions, containing adipose progenitor cells, may boost the
efﬁcacy and safety of conventional autologous micro-fat grafting.
 ASCs are a promising adult stem/progenitor cell population for use as a therapeutic tool, especiallyin the initial stages of regenerative medicine. A substantial (therapeutic) amount of cells can beobtained without cell culture and the anticipated therapeutic potential is similar to that of bonemarrow-derived mesenchymal stem cells.

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Future perspective
Literature reports of ASCs have increased rapidly in the last 3 years and are continuing torise. More than ten kinds of clinical trials using
freshly isolated or cultured ASCs are ongoing in
more than ten countries. Clinical applications
are designed based on either (or both) potential ASC differentiation into adipose, vasculature and heart muscle, or the secretory capacityof ASCs for growth factors or hormones. New
strategies will be developed to maximize thetherapeutic potential of adult stem cells; likely,a microenvironment will be produced to activate and control the administrated cells. Suchmicroenvironments can be prepared by developing novel methods of cell administrationor preconditioning of the recipient tissue, forexample, combined administration with bioscaffolds (e.g., tissues, cells, extracellular matrix ortheir combined constructs) or factor-releasing

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8Papers of special note have been highlighted as:
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Financial & competing interests disclosure
The authors have no relevant afﬁliations or ﬁnancial
involvement with any organization or entity with a ﬁnancial interest in or ﬁnancial conﬂict with the subject matteror materials discussed in the manuscript. This includes
employment, consultancies, honoraria, stock ownership or
options, expert testimony, grants or patents received or
pending, or royalties.
No writing assistance was utilized in the production ofthis manuscript.

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Adipose-derived stem/progenitor cells

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Adipocyte progenitor cells resident inmurine adipose tissue were identiﬁed as
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Cao Y, Sun Z, Liao L et al.: Human adipose
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REVIEW

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Muthukrishnan L, Warder E, McNeil PL:
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Myolotte LA, Duffy AM, Murphy M et al.:Metabolic ﬂexibility permits mesenchymal
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Zengin E, Chalajour F, Gehling UM et al.:Vascular wall resident progenitor cells:a source for postnatal vasculogenesis.
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Endothelial stem/progenitor cells areresident at the transitional area from thesmooth muscle layer to the adventitial layerof vascular walls.

Moseley TA, Zhu M, Hedrick MH: Adiposederived stem and progenitor cells as ﬁllers inplastic and reconstructive surgery. Plast. Reconstr.
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Yoshimura K, Aoi N, Suga H et al.: Ectopic
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Traktuev DO, Merfeld-Clauss S, Li J et al.:A population of multipotent CD34-positive
adipose stromal cells share pericyte andmesenchymal surface markers, reside in aperiendothelial location, and stabilize
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Amos PJ, Shang H, Bailey AM, Taylor A,
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3(3), 301–313 (2008).

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Human mesenchymal stem cells foundthroughout fetal and adult tissues aresuggested to be perivascular cells (pericytes).

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Tang W, Zeve D, Suh JM et al.: Whitefat progenitor cells reside in the adipose
vasculature. Science 322(5901), 583–586 (2008)

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Adipocyte progenitor cells reside in the muralcell compartment of the adipose vasculature.

www.futuremedicine.com

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National plastic surgery statistics 2007.
www.plasticsurgery.org/media/statistics/
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cfm&PageID=29287

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