Adipose-derived Stem cells and BMP2: Part 2. BMP2 may not influence the osteogenic fate of human adipose-derived stem cells

Abstract

Although recent studies have proposed that human adipose-derived stem cells (ASCs), together with BMP2, can heal critical-sized bony defects, a companion study in this issue suggests that ASCs may not respond to BMP2 in vivo. To examine why this may be occurring. ASCs were treated with BMP2 and the cells' in vitro osteogenic capacity assessed along with the canonical BMP2 signaling pathway. In vitro treatment of ASCs with BMP2 had no consistent and significant effect on matrix mineralization or their expression of several osteogenic markers. Consistent and significant changes to Smad1/5/8 phosphorylation levels were also not observed upon BMP2 induction. The removal of dexamethasone from the BMP2 induction conditions had no effect on the observed results nor did stimulating ASCs with BMP2 from an alternate source (INFUSE; Medtronic, Minneapolis, MN, USA). In addition, no BMP-induced nuclear translocation of Smad1/Smad4 complexes could be discerned, suggesting that the canonical BMP2 signaling pathway may not be functional in ASCs. Interestingly, three downstream BMP2 pathway genes, distal-less3 (dlx3), distal-less5 (dlx5), and osterix, were not expressed in BMP2-induced ASCs, calling the utility of BMP2 induced in ASCs into question. The results of this in vitro study were consistent with that of our companion in vivo study that suggests a lack of effect of BMP2 on the osteogenic capacity of ASCs. Taken together, the data from both studies suggest that ASC osteogenic differentiation may not be influenced by BMP2. Consequently, combining BMP2 treatment with adult stem cells, like ASCs, may not be a viable strategy for bony healing.

Keywords:

• rhBMP2
• tissue engineering
• adipose-derived stem cells
• femoral defect
• bone formation

Acknowledgments

A portion of this work was supported by the National Institutes of Health grant R01AR47637 (National Institute of Arthritis, Musculoskeletal and Skin Disorders, PI; Benhaim, P) and the National Institutes of Health R21DE018494 (National Institute of Dental and Craniofacial Research/NIDCR, PI: Zuk P, Co-PI: Wu, B). Dr. Zuk's work has significantly contributed to a patent regarding the isolation and use of ASCs. Dr. Prosper Benhaim is also listed as an inventor on this patent. However, neither Dr. Zuk nor Dr. Benhaim has any financial interest in the work presented in this article.