Title

Serum-Deprived Human Multipotent Mesenchymal Stromal cells (MSCs) are Highly Angiogenic.

Funding Source

National Institutes of Health

Grant Number

P40RR017447,AR 47796,AR 48323

Department

Department of Biology

Document Type

Article

Publication Date

5-2011

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.

Comments

DOI: 10.1016/j.scr.2011.01.004

PubMed ID: 21421339

Funding text

Some of the materials employed in this work were provided by the Tulane Center for Gene Therapy through a grant from NCRR of the NIH , Grant P40RR017447 and Grants NIH AR 47796 and AR 48323 , the Oberkotter Foundation, the HCA the Health Care Company, and the Louisiana Gene Therapy Research Consortium to Dr. Darwin J. Prockop. We also thank Mr. Patrice Penfornis for technical assistance and Margaret Wolf for critical review of the manuscript.

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