Paracrine Factors Secreted by Umbilical Cord-Derived Mesenchymal Stem Cells Induce Angiogenesis In Vitro by a VEGF-Independent Pathway

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 proangiogenic factors in the conditioned media (CM) derived from UCMSCs by ELISA. While vascular endothelial growth factor (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 exposed in vitro to CM, in comparison to control media, showed improved migration (P < 0.007) and capillary-like network formation (P < 0.001) 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 and matrix metalloproteases-2 (237.4 -47

Human umbilical cord mesenchymal stem cells: an overview of their potential in cell-based therapy

“…They manifest that HUC-MSCs can secrete an extensive variety of growth factors, cytokines, and chemokines including quantities of hepatocyte growth factor, stromal-derived factor-1 and monocyte chemotactic protein-1, vascular endothelial growth factor, insulin-like growth factor-1, interleukin-8, brainderived neurotrophic factor and glial cell-derived neurotrophic factor (GDNF), etc. [81,82]. These released factors may make contributions to preventing the adjacent cells from apoptosis, promoting angiogenesis, modulating inflammation and activating the intra-stem cells, which help to create a friendly environment for intrinsic restorative processes [83].…”

The efficacy of Schwann cell transplantation on motor function recovery after spinal cord injuries in animal models: A systematic review and meta-analysis

“…Transplantation of these cells can decrease proliferation of glial cells and improve recovery by biologically active molecules through regulating release of cytokines and growth factors. Furthermore, their role in vascularization might induce generation of new vasculature in the spine (Hua et al, 2014;Kuchroo et al, 2014).…”

Tissue-specific angiogenic and invasive properties of human neonatal thymus and bone MSCs: Role of SLIT3-ROBO1

“…3.2 | Neonatal thymus MSCs are more proangiogenic than subject-matched nbMSCs After identifying that ntMSCs and nbMSCs possessed different pericytic signatures, we next assessed if ntMSCs would be functionally different than subject-matched nbMSCs in promoting neovascularization in vitro and in vivo. Because the primary mechanism by which MSCs stimulate angiogenesis is thought to be via the secretion of proangiogenic factors, 40,41 we first determined if the secretome from these two types of MSCs would vary in their ability to promote HUVEC tube formation in vitro. HUVECs in Matrigel were exposed to CM obtained from ntMSC and nbMSC cultures.…”