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Regulation of Human Adipose-Derived Stromal Cell Osteogenic Differentiation by Insulin-Like Growth Factor-1 and Platelet-Derived Growth Factor-α

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

Plastic and Reconstructive Surgery: July 2010 - Volume 126 - Issue 1 - p 41-52
doi: 10.1097/PRS.0b013e3181da8858
Experimental: Original Articles

Background: Human adipose-derived stromal cells possess a great potential for tissue engineering purposes. The authors' laboratory is interested in harnessing human adipose-derived stromal cells for skeletal tissue regeneration and identifying those factors that enhance human adipose-derived stromal cell osteogenic differentiation. The authors hypothesized that insulin-like growth factor (IGF) and platelet-derived growth factor (PDGF) would stimulate human adipose-derived stromal cell osteogenesis and that IGF would stimulate adipogenesis.

Methods: Adipose-derived stromal cells were harvested from human lipoaspirate. Previously, a microarray analysis examined gene expression throughout osteogenic differentiation. In a candidate fashion, the authors added recombinant IGF-1 and PDGF-α individually and in combination. Osteogenesis and adipogenesis were assessed by alkaline phosphatase, alizarin red, and oil red O staining, and quantitative real-time polymerase chain reaction (RUNX2, ALP, OCN, IGF1, PPARG, LPL, AP2, and GCP1). Finally, intersection between IGF and PDGF signaling pathways was evaluated.

Results: IGF-1 was observed to increase osteogenic differentiation by all markers (p < 0.01). However, PDGF-α when added alone primarily did not affect osteogenic markers. PDGF-α positively regulated transcription of IGF1. Addition of PDGF-α in combination with or before IGF-1 enhanced osteogenesis more than either alone. IGF-1 increased whereas PDGF-α diminished human adipose-derived stromal cell adipogenesis.

Conclusions: IGF signaling significantly increased osteogenesis in human adipose-derived stromal cells and may be used for tissue-engineering purposes. The combination of PDGF and IGF may be more beneficial than either alone in driving adipose-derived stromal cell osteogenesis. Future in vivo applications will focus on the combination of adipose-derived stromal cells, biomimetic scaffolds, and recombinant IGF.

Stanford, Calif.

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

Received for publication November 5, 2009; accepted January 4, 2010.

The first two authors contributed equally to this article.

Disclosure: The authors have no financial interest in any of the products, devices, procedures, or anything else connected with the article. No internal or external funding was received to complete this study.

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

©2010American Society of Plastic Surgeons