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Depot-Specific Variation in the Osteogenic and Adipogenic Potential of Human Adipose-Derived Stromal Cells

Levi, Benjamin M.D.; James, Aaron W. B.A.; Glotzbach, Jason P. M.D.; Wan, Derrick C. M.D.; Commons, George W. M.D.; Longaker, Michael T. M.D., M.B.A.

Plastic and Reconstructive Surgery: September 2010 - Volume 126 - Issue 3 - p 822-834
doi: 10.1097/PRS.0b013e3181e5f892
Experimental: Original Articles

Background: Adipose-derived stromal cells hold promise for use in tissue regeneration. However, multiple facets of their biology remain unclear. The authors examined the variations in osteogenesis and adipogenesis in adipose-derived stromal 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 patients). Osteogenic and adipogenic differentiation was performed (alkaline phosphatase, 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 adipogenic 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 expressed in flank-derived adipose-derived stromal cells.

Conclusions: Variations exist between fat depots in terms of adipose-derived stromal 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.

Stanford and Los Angeles, Calif.

From the Hagey Pediatric Regenerative Medicine Research Laboratory, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, 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.

Disclosure: The authors have no financial interest in any of the products, devices, procedures, or anything else connected with the article.

Michael T. Longaker, M.D., M.B.A., Hagey Pediatric Regenerative Medicine Research Laboratory, Stanford University School of Medicine, 257 Campus Drive, Stanford University, Stanford, Calif. 94305-5148,

©2010American Society of Plastic Surgeons