EXPERIMENTAL
Depot-Specific Variation in the Osteogenic and
Adipogenic Potential of Human Adipose-Derived
Stromal Cells
Benjamin Levi, M.D.
Aaron W. James, B.A.
Jason P. Glotzbach, M.D.
Derrick C. Wan, M.D.
George W. Commons, M.D.
Michael T. Longaker, M.D.,
M.B.A.
Stanford and Los Angeles, Calif.
Background: Adipose-derived stromal cells hold promise for use in tissue regen-
eration. However, multiple facets of their biology remain unclear. The authors
examined the variations in osteogenesis and adipogenesis in adipose-derived stro-
mal cells between subcutaneous fat depots and potential molecular causes.
Methods: Adipose-derived stromal cells were isolated from human patients from
subcutaneous fat depots, including arm, flank, thigh, and abdomen (n = 5 pa-
tients). Osteogenic and adipogenic differentiation was performed (alkaline phos-
phatase, alizarin red, and oil red O staining, and quantitative real-time polymerase
chain reaction). Co-cultures were established to assess the paracrine effect of human
adipose-derived stromal cells on mouse osteoblasts. Finally, HOX gene expression
was analyzed by quantitative real-time polymerase chain reaction.
Results: Subcutaneous fat depots retain markedly different osteogenic and adipo-
genic potentials. Osteogenesis was most robust in adipose-derived stromal cells from
the flank and thigh, as compared with those from the arm and abdomen (p 0.05
by all markers examined). This was accompanied by elevations of BMP4 and
BMPR1B (p 0.05 by all markers examined). The osteogenic advantage of cells
from the flank and thigh was again observed when analyzing the paracrine effects
of these cells. Conversely, those cells isolated from the flank had a lesser ability to
undergo adipogenic differentiation. Adipose-associated HOX genes were less ex-
pressed in flank-derived adipose-derived stromal cells.
Conclusions: Variations exist between fat depots in terms of adipose-derived stro-
mal cell osteogenic and adipogenic differentiation. Differences in HOX expression
and bone morphogenetic protein signaling may underlie these observations. This
study indicates that the choice of fat depot derivation of adipose-derived stromal
cells may be an important one for future efforts in tissue engineering. (Plast.
Reconstr. Surg. 126: 822, 2010.)
C
omposite tissue reconstruction remains a
significant challenge in the treatment of pa-
tients after traumatic injuries, oncologic re-
sections, and congenital anomalies. Synthetic ma-
terials and autogenous grafts are currently used to
reconstruct skeletal defects, but they are limited by
hardware failure, infection, and graft resorption.
1
In addition, bone marrow is less readily available
than subcutaneous adipose tissue for the healing
of larger defects.
2
Fat transfer for the purposes
of soft-tissue augmentation suffers from equal
disadvantages.
3
Grafts have been shown to be rela-
tively unreliable over time because of resorption.
4
For example, in craniofacial fat transfer, it has been
difficult to demonstrate long-term success.
3
It is
against the backdrop of the shortcomings of skeletal
and soft-tissue reconstruction that our laboratory is
interested in the use of adipose-derived stromal cells
for both skeletal and soft-tissue regeneration.
From the Hagey Pediatric Regenerative Medicine Research
Laboratory, Department of Surgery, Plastic and Reconstruc-
tive Surgery Division, Stanford University School of Medi-
cine, and the Division of Plastic and Reconstructive Surgery,
University of California, Los Angeles.
Received for publication January 28, 2010; accepted March
5, 2010.
The first two authors share equal responsibility in the work
presented in this article.
Copyright ©2010 by the American Society of Plastic Surgeons
DOI: 10.1097/PRS.0b013e3181e5f892
Disclosure: The authors have no financial interest
in any of the products, devices, procedures, or any-
thing else connected with the article.
www.PRSJournal.com 822