title: Platelet-Derived Growth Factor BB Enhances Osteogenesis of Adipose-Derived But Not Bone Marrow-Derived Mesenchymal Stromal/Stem Cells.
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.
authors.affiliation: Department of Biomedical Engineering.|Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Ben P
authors.initials: BP
authors.lastname: Hung
authors.affiliation: Department of Biomedical Engineering.|Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Daphne L
authors.initials: DL
authors.lastname: Hutton
authors.affiliation: Department of Biomedical Engineering.|Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Kozielski
authors.affiliation: Department of Biomedical Engineering.|Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Bishop
authors.affiliation: Fischell Department of Biomedical Engineering, University of Maryland, College Park, Maryland, USA.
authors.forename: Bilal
authors.initials: B
authors.lastname: Naved
authors.affiliation: Department of Biomedical Engineering.|Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jordan J
authors.initials: JJ
authors.lastname: Green
authors.affiliation: Department of Biology, Case Western Reserve University, Cleveland, Ohio, USA.
authors.forename: Arnold I
authors.initials: AI
authors.lastname: Caplan
authors.affiliation: Department of Medicine and Surgery, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.affiliation: Department of Plastic Surgery, The Johns Hopkins Hospital, Baltimore, Maryland, USA.
authors.forename: Amir H
authors.initials: AH
authors.lastname: Dorafshar
authors.affiliation: Department of Biomedical Engineering.|Translational Tissue Engineering Center, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Materials Science & Engineering, The Johns Hopkins University Whiting School of Engineering, Baltimore, Maryland, USA.
authors.forename: Warren L
authors.initials: WL
authors.lastname: Grayson
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D000328:Adult; D000818:Animals; D000077214:Becaplermin; D001853:Bone Marrow / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis / Q000494:pharmacology*; D012886:Skull / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods
chemical_list: D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin
keywords: Bone; Platelet-derived growth factor; Stem cells; Tissue engineering