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

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Abstract
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.

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