BMP-2 does not influence the osteogenic fate of human adipose-derived stem cells.
Autor: | Grewal NS; Los Angeles, Calif. From the Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine at University of California, Los Angeles., Gabbay JS, Ashley RK, Wasson KL, Bradley JP, Zuk PA |
---|---|
Jazyk: | angličtina |
Zdroj: | Plastic and reconstructive surgery [Plast Reconstr Surg] 2009 Feb; Vol. 123 (2 Suppl), pp. 158S-165S. |
DOI: | 10.1097/PRS.0b013e318191c844 |
Abstrakt: | Background: Recent studies have shown that bone morphogenetic protein (BMP)-2, a potent osteogenic growth factor, in combination with human adipose-derived stem cells can heal critical-sized bony defects. However, whether BMP-2 induces an osteogenic response in the adipose-derived stem cells remains unknown. Methods: : In vitro calcium production, osteogenic gene expression, and BMP-2 receptor expression on the adipose-derived stem cell surface were analyzed in BMP-2-stimulated adipose-derived stem cells. The cells (2 x 10(7) cells) maintained in osteogenic medium were treated with an initial pulse of BMP-2 for 48 hours or 7 days or were given continuous BMP-2. To assess the response of these cells to BMP-2 in vivo, they (250,000 cells) were seeded into polylactic-co-glycolic acid (PLGA) collagraft scaffolds treated with 5 microg of BMP-2 and implanted into critical-sized femoral rat defects (n = 40). Healing was assessed histologically and quantitated by micro-computed tomography. Results: In vitro treatment of adipose-derived stem cells with BMP-2 revealed decreased ability of the cells to undergo matrix calcification, demonstrated by decreased calcium production and decreased osteogenic gene expression of transcription factor Cbfa-1 and key extracellular proteins. Flow cytometry demonstrated decreased expression of BMP-2 receptors 1a and 1b in osteogenically differentiated adipose-derived stem cells stimulated with BMP-2. In vivo implantation of adipose-derived stem cell-seeded PLGA did not result in healing of critical-sized femoral defects in rodents, whereas implantation of BMP-2-absorbed PLGA, with or without adipose-derived stem cells, consistently healed these defects. Conclusions: The data suggests that osteogenic differentiation of adipose-derived stem cells is marginally affected by the addition of BMP-2. Consequently, stem cells in combination with BMP-2 may not be a viable strategy for the bony healing. |
Databáze: | MEDLINE |
Externí odkaz: |