BMP-2 does not influence the osteogenic fate of human adipose-derived stem cells.
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.
Grewal
Navanjun S
NS
Los Angeles, Calif. From the Division of Plastic and Reconstructive Surgery, David Geffen School of Medicine at University of California, Los Angeles.
Gabbay
Joubin S
JS
Ashley
Rebekah K
RK
Wasson
Kristy L
KL
Bradley
James P
JP
Zuk
Patricia A
PA
D000273:Adipose Tissue; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D051381:Rats; D013234:Stem Cells / Q000187:drug effects
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D036341:Intercellular Signaling Peptides and Proteins