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Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
Department of Orthopaedic Surgery, Division of Orthopaedic Surgery, Duke University Medical Center, Durham, NC, USA
Summary
Adipose tissue is an abundant, accessible, and replenishable source of
adult stem cells that can be isolated from liposuction waste tissue by
collagenase digestion and differential centrifugation. These adiposederived adult stem (ADAS) cells are multipotent, differentiating along
the adipocyte, chondrocyte, myocyte, neuronal, and osteoblast lineages,
and can serve in other capacities, such as providing hematopoietic
support and gene transfer. ADAS cells have potential applications for
the repair and regeneration of acute and chronically damaged tissues.
Additional pre-clinical safety and efficacy studies will be needed before
the promise of these cells can be fully realized.
Introduction
Keywords
adipose tissue, stem cell, multipotent, tissue engineering.
Correspondence to: Jeffrey M Gimble, Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Rd, Baton Rouge, LA
70808, USA.
2003 ISCT
DOI: 10.1080/14653240310003026
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Soft tissues
Adipocyte */ soft tissue cosmesis
Human ADAS cells have the ability to return to what is
believed to be their original differentiation pathway,
adipogenesis. This is accomplished in vitro using induction
cocktails containing insulin, methylisobutylxanthine (a
phosphodiesterase inhibitor resulting in elevated cyclic
AMP levels), hydrocortisone or dexamethasone (a glucocorticoid receptor agonist), indomethacin or thiazolidinedione (a peroxisome proliferator activated receptor g
ligand), pantothenate, biotin, and/or triiodothyronine
[20,21,24,25,30,43]. After 7 /10 days, the human ADAS
cells contain vacuoles filled with neutral lipid, as detected
by Oil Red O or Nile Red staining, secrete increased
amounts of the adipocyte protein leptin, and transcribe
adipogenic mRNAs such as the fatty acid binding protein,
aP2, and lipoprotein lipase [21,24,25,30,43]. Some of these
parameters (leptin, aP2 mRNA levels) have been quantified and found to increase by several hundred-fold during
the differentiation process [24,43].
When grown on appropriate biomaterial scaffolds,
ADAS cells form new fat depots in vivo. In a variety of
animal models (murine, porcine), undifferentiated and/or
adipocyte differentiated ADAS cells have been implanted
s.c. with alginate coupled to RGD peptides, collagen, fibrin
glue, hyaluronic acid, poly glycolic acid/ poly lactic acid
(PGLA), and polytetrafluoroethylene to form fat [44 /52].
It is likely that the ability of nutrients to reach the
embedded ADAS cells influences their differentiation.
Studies demonstrate that biomaterials with greater porosity display improved adipogenic function in vivo [46]. In
nude mice, human preadipocytes performed better in
terms of adipocyte differentiation when loaded into a
porous hyaluronate sponge compared to denser unwoven
hyaluronate or collagen sponges [46]. With further refinement, it may be possible to use these approaches for
clinical cosmetic and reconstructive procedures.
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Conclusions
One of the major challenges facing the emerging field of
regenerative medicine is a reliable source of cells for tissue
repair. Human ADAS cells meet many of the requirements
required of the ideal cell for tissue engineering. They are
available in quantities of hundreds of million cells
per individual, accessible through a relatively noninvasive method, can differentiate along multiple celllineage pathways, are transplantable in an autologous
manner, and could be manufactured in a controlled,
large-scale manner in accordance with regulatory guidelines.
Further studies are necessary before ADAS cells can be
used clinically. In particular, investigators need to demonstrate the safety and efficacy of ADAS cells in animal
models, either alone or in combination with biomaterial
scaffolds. In addition, manufacturing and quality assurance
issues need to be addressed. Although challenges remain,
the ADAS cell holds significant promise for future
applications.
Acknowledgements
The authors acknowledge support from the following
granting agencies: Artecel Sciences, Inc., the North
Carolina Biotechnology Center, the Kenan Instititute for
367
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