Serum-deprived human multipotent mesenchymal stromal cells (MSCs) are highly angiogenic

Stem Cell Res. 2011 May;6(3):215-25. doi: 10.1016/j.scr.2011.01.004. Epub 2011 Jan 31.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiogenesis Inducing Agents / metabolism*
  • Angiogenesis Inducing Agents / pharmacology
  • Animals
  • Aorta / drug effects
  • Cell Differentiation
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply
  • Chorioallantoic Membrane / drug effects
  • Culture Media, Conditioned / metabolism
  • Culture Media, Serum-Free / metabolism
  • Humans
  • In Vitro Techniques
  • Multipotent Stem Cells / cytology
  • Multipotent Stem Cells / metabolism*
  • Neovascularization, Physiologic / drug effects*
  • Rats
  • Rats, Wistar
  • Stromal Cells / cytology
  • Stromal Cells / metabolism*

Substances

  • Angiogenesis Inducing Agents
  • Culture Media, Conditioned
  • Culture Media, Serum-Free