Regulation of Human Adipose-derived Stromal Cell Osteogenic Differentiation by Insulin-like Growth Factor-1 and Platelet-derived Growth Factor-alpha

Overview

Journal Plast Reconstr Surg

Specialty General Surgery

Date 2010 Mar 12

PMID 20220555

Citations 24

Authors

Benjamin Levi

Aaron W James

Derrick C Wan

Jason P Glotzbach

George W Commons

Michael T Longaker

Affiliations

Soon will be listed here.

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-alpha 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-alpha when added alone primarily did not affect osteogenic markers. PDGF-alpha positively regulated transcription of IGF1. Addition of PDGF-alpha in combination with or before IGF-1 enhanced osteogenesis more than either alone. IGF-1 increased whereas PDGF-alpha 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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