title: Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic.
abstract: Recent reports have indicated that mesenchymal stromal cells (MSCs) from bone marrow have a potential in vascular remodeling and angiogenesis. Here, we report a unique phenomenon that under serum-deprived conditions MSCs survive and replicate. Secretome analysis of MSCs grown under serum-deprived conditions (SD-MSCs) identified a significant upregulation of prosurvival and angiogenic factors including VEGF-A, ANGPTs, IGF-1, and HGF. An ex vivo rat aortic assay demonstrated longer neovascular sprouts generated from rat aortic rings cultured in SD-MSC-conditioned media compared to neovascular sprouts from aortas grown in MSC-conditioned media. With prolonged serum deprivation, a subpopulation of SD-MSCs began to exhibit an endothelial phenotype. This population expressed endothelial-specific proteins including VEGFR2, Tie2/TEK, PECAM/CD31, and eNOS and also demonstrated the ability to uptake acetylated LDL. SD-MSCs also exhibited enhanced microtubule formation in an in vitro angiogenesis assay. Modified chick chorioallantoic membrane (CAM) angiogenesis assays showed significantly higher angiogenic potential for SD-MSCs compared to MSCs. Analysis of CAMs grown with SD-MSCs identified human-specific CD31-positive cells in vascular structures. We conclude that under the stress of serum deprivation MSCs are highly angiogenic and a population of these cells has the potential to differentiate into endothelial-like cells.
authors.affiliation: Center for Gene Therapy, Tulane University Health Science Center, New Orleans, LA 70118, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Oskowitz
authors.forename: Harris
authors.initials: H
authors.lastname: McFerrin
authors.forename: Miriam
authors.initials: M
authors.lastname: Gutschow
authors.forename: Mary Leita
authors.initials: ML
authors.lastname: Carter
authors.forename: Radhika
authors.initials: R
authors.lastname: Pochampally
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D002454:Cell Differentiation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D039902:Multipotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free