title: Traumatized muscle-derived multipotent progenitor cells recruit endothelial cells through vascular endothelial growth factor-A action.
abstract: Traumatized muscle, such as that debrided from blast injury sites, is considered a promising and convenient tissue source for multipotent progenitor cells (MPCs), a population of adult mesenchymal stem cell (MSC)-like cells. The present study aimed to assess the regenerative therapeutic potential of human traumatized muscle-derived MPCs, e.g., for injury repair in the blast-traumatized extremity, by comparing their pro-angiogenic potential in vitro and capillary recruitment activity in vivo to those of MSCs isolated from human bone marrow, a widely-used tissue source. MPCs were tested for their direct and indirect effects on human microvascular endothelial cells (ECs) in vitro. The findings reported here showed that MPC-conditioned culture medium (MPC-CM), like MSC-CM, promoted EC-cord network branching. Silent (si)RNA-mediated silencing of vascular endothelial growth factor-A (VEGF-A) expression in MPCs attenuated this effect. In a chick embryonic chorioallantoic membrane in vivo angiogenesis assay, MPCs encapsulated in photocrosslinked gelatin scaffold recruited blood vessels more efficiently than either MSCs or human foreskin fibroblasts. Together, these findings support the potential application of traumatized muscle-derived MPCs in cell-based regenerative medicine therapies as a result of their influence on EC organization. Copyright © 2017 John Wiley & Sons, Ltd.
authors.affiliation: Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, School of Medicine.|Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Heidi R H
authors.identifier: 0000-0001-7088-3732
authors.initials: HRH
authors.lastname: Supanc
authors.affiliation: Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Gorman
authors.affiliation: Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, School of Medicine.|Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001753:Blast Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D002642:Chick Embryo; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D044968:Regenerative Medicine; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: chorioallantoic membrane assay; endothelial cells; endothelial cord-formation; mesenchymal stem cells; photocrosslinked polymer; siRNA gene silencing