Platelet-Derived Growth Factor BB Enhances Osteogenesis of Adipose-Derived but Not Bone Marrow-Derived Mesenchymal Stromal/Stem Cells

Ben P. Hung, Daphne L. Hutton, Kristen L. Kozielski, Corey J. Bishop, Bilal Naved, Jordan J. Green, Arnold I. Caplan, Jeffrey M. Gimble, Amir H. Dorafshar, Warren L. Grayson

Research output: Contribution to journalArticle

Abstract

Tissue engineering using mesenchymal stem cells (MSCs) holds great promise for regenerating critically sized bone defects. While the bone marrow-derived MSC is the most widely studied stromal/stem cell type for this application, its rarity within bone marrow and painful isolation procedure have motivated investigation of alternative cell sources. Adipose-derived stromal/stem cells (ASCs) are more abundant and more easily procured; furthermore, they also possess robust osteogenic potency. While these two cell types are widely considered very similar, there is a growing appreciation of possible innate differences in their biology and response to growth factors. In particular, reports indicate that their osteogenic response to platelet-derived growth factor BB (PDGF-BB) is markedly different: MSCs responded negatively or not at all to PDGF-BB while ASCs exhibited enhanced mineralization in response to physiological concentrations of PDGF-BB. In this study, we directly tested whether a fundamental difference existed between the osteogenic responses of MSCs and ASCs to PDGF-BB. MSCs and ASCs cultured under identical osteogenic conditions responded disparately to 20 ng/ml of PDGF-BB: MSCs exhibited no difference in mineralization while ASCs produced more calcium per cell. siRNA-mediated knockdown of PDGFRβ within ASCs abolished their ability to respond to PDGF-BB. Gene expression was also different; MSCs generally downregulated and ASCs generally upregulated osteogenic genes in response to PDGF-BB. ASCs transduced to produce PDGF-BB resulted in more regenerated bone within a critically sized murine calvarial defect compared to control ASCs, indicating PDGF-BB used specifically in conjunction with ASCs might enhance tissue engineering approaches for bone regeneration. Stem Cells 2015;33:2773-2784

Original languageEnglish (US)
Pages (from-to)2773-2784
Number of pages12
JournalStem Cells
Volume33
Issue number9
DOIs
StatePublished - Sep 1 2015

Keywords

  • Bone
  • Platelet-derived growth factor
  • Stem cells
  • Tissue engineering

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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    Hung, B. P., Hutton, D. L., Kozielski, K. L., Bishop, C. J., Naved, B., Green, J. J., Caplan, A. I., Gimble, J. M., Dorafshar, A. H., & Grayson, W. L. (2015). Platelet-Derived Growth Factor BB Enhances Osteogenesis of Adipose-Derived but Not Bone Marrow-Derived Mesenchymal Stromal/Stem Cells. Stem Cells, 33(9), 2773-2784. https://doi.org/10.1002/stem.2060