Stem Cells Dev. 2014 Sep 17. [Epub ahead of print]

Paracrine Factors Secreted by Umbilical Cord Derived Mesenchymal Stem Cells Induce Angiogenesis in vitro by a VEGF-independent Pathway.

Ghosh D¹, Kuchroo P, Dave V, Vijayan A, Viswanathan C.

Abstract

Improvement in angiogenesis using mesenchymal stem cells (MSCs) is evolving as an option in patients with vascular insufficiencies. The paracrine factors secreted by MSCs have been attributed to the angiogenic response. This study was conducted to identify the factors secreted by umbilical cord derived-MSCs (UCMSCs) that might play a role in angiogenesis. To this aim, we evaluated the presence of well known pro-angiogenic factors in the conditioned media (CM) derived from UCMSCs by ELISA. While VEGF, a well known angiogenic factor was not detected in the CM, gene expression was nevertheless detected in these cells. Further investigations revealed the presence of soluble VEGF receptors (sVEGF -R1 and R2) that were capable of neutralizing exogenous VEGF. Human umbilical cord vein derived endothelial cells (HUVEC) exposed in vitro to CM, in comparison to control media showed improved migration and capillary-like network formation with no significant change in endothelial cell proliferation. The angiogenic response observed with the paracrine factors secreted by UCMSC could be due to the presence of significant levels of a metalloprotease, MMP-2 (237.4 ± 47.1ng/10^6 cells). Data suggests that a VEGF-independent pathway is involved in the angiogenic response observed with endothelial cells in presence of UCMSC-CM.