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FASEB J. 2016 Jan;30(1):477-86. doi: 10.1096/fj.15-279984. Epub 2015 Oct 6.

Hydrogel biophysical properties instruct coculture-mediated osteogenic potential.

Author information

1
*Department of Biomedical Engineering and Department of Orthopaedic Surgery, School of Medicine, University of California, Davis, Davis, California, USA; and Department of Biophysics, Federal University of Sao Paulo, Sao Paulo, Brazil.
2
*Department of Biomedical Engineering and Department of Orthopaedic Surgery, School of Medicine, University of California, Davis, Davis, California, USA; and Department of Biophysics, Federal University of Sao Paulo, Sao Paulo, Brazil jkleach@ucdavis.edu.

Abstract

Cell-based approaches for bone formation require instructional cues from the surrounding environment. As an alternative to pharmacological strategies or transplanting single cell populations, one approach is to coimplant populations that can establish a new vasculature and differentiate to bone-forming osteoblasts. Mesenchymal stem/stromal cells (MSCs) possess osteogenic potential and produce numerous angiogenic growth factors. Endothelial colony-forming cells (ECFCs) are a subpopulation of endothelial progenitor cells capable of vasculogenesis in vivo and may provide endogenous cues to support MSC function. We investigated the contribution of the carrier biophysical properties to instruct entrapped human MSCs and ECFCs to simultaneously promote their osteogenic and proangiogenic potential. Compared with gels containing MSCs alone, fibrin gels engineered with increased compressive stiffness simultaneously increased the osteogenic and proangiogenic potential of entrapped cocultured cells. ECFCs produced bone morphogenetic protein-2 (BMP-2), a potent osteoinductive molecule, and increases in BMP-2 secretion correlated with gel stiffness. Coculture of MSCs with ECFCs transduced to knockdown BMP-2 production abrogated the osteogenic response to levels observed with MSCs alone. These results demonstrate that physical properties of engineered hydrogels modulate the function of cocultured cells in the absence of inductive cues, thus increasing the translational potential of coimplantation to speed bone formation and repair.

KEYWORDS:

BMP-2; ECFC; fibrin; mesenchymal stem cell; osteogenesis

PMID:
26443826
PMCID:
PMC4684517
DOI:
10.1096/fj.15-279984
[Indexed for MEDLINE]
Free PMC Article

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