title: 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±47.1 ng/10(6) cells). Data suggest that a VEGF-independent pathway is involved in the angiogenic response observed with endothelial cells in the presence of UCMSC-CM.
authors.affiliation: Tissue Engineering Group, Regenerative Medicine, Reliance Life Sciences Pvt. Ltd. , Navi-Mumbai, Maharashtra, India .
authors.forename: Pushpa
authors.initials: P
authors.lastname: Kuchroo
authors.forename: Viral
authors.initials: V
authors.lastname: Dave
authors.forename: Ajay
authors.initials: A
authors.lastname: Vijayan
authors.forename: Chandra
authors.initials: C
authors.lastname: Viswanathan
authors.forename: Deepa
authors.initials: D
authors.lastname: Ghosh
mesh_terms: D002465:Cell Movement; D017077:Culture Media, Conditioned / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2