Hydrogel biophysical properties instruct coculture-mediated osteogenic potential

Hydrogel biophysical properties instruct coculture-mediated osteogenic potential

Author Murphy, Kaitlin C. Google Scholar
Stilhano, Roberta S. Autor UNIFESP Google Scholar
Mitra, Debika Google Scholar
Zhou, Dejie Google Scholar
Batarni, Samir Google Scholar
Silva, Eduardo A. Google Scholar
Leach, J. Kent Autor UNIFESP Google Scholar
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 fibrin
mesenchymal stem cell
ECFC
BMP-2
osteogenesisEndothelial Progenitor Cells
Mesenchymal Stem-Cells
Marrow Stromal Cells
Colony-Forming Cells
Acid-Based Hydrogel
Bone Regeneration
Fibrin Gels
In-Vivo
Capillary Morphogenesis
Bioactive Glass
Language English
Sponsor U.S. National Institutes of Health
National Institute of Dental and Craniofacial Research [R03-DE021704]
AO Foundation (Davos, Switzerland) [C10-39L]
American Heart Association Western States Affiliate Pre-doctoral Fellowship
Grant number U.S. National Institutes of Health, National Institute of Dental and Craniofacial Research Grant R03-DE021704, and the AO Foundation (Davos, Switzerland) (C10-39L to J.K.L.). K.M. was supported by the American Heart Association Western States Affiliate Pre-doctoral Fellowship
Date 2016
Published in Faseb Journal. Bethesda, v. 30, n. 1, p. 477-486, 2016.
ISSN 0892-6638 (Sherpa/Romeo, impact factor)
Publisher Federation Amer Soc Exp Biol
Extent 477-486
Origin http://dx.doi.org/10.1096/fj.15-279984
Access rights Closed access
Type Article
Web of Science ID WOS:000367621000044
URI http://repositorio.unifesp.br/handle/11600/46063

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