Open AccessA Subset of Paracrine Factors as Efficient Biomarkers for Predicting Vascular Regenerative Efficacy of Mesenchymal Stromal/Stem Cells
Author(s) -
Kim HyunKyung,
Lee SeulGi,
Lee SeungWoo,
Oh Bae Jun,
Kim Jae Hyeon,
Kim Jeong A.,
Lee Guisera,
Jang JaeDeog,
Joe Young Ae
Publication year - 2019
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2920
Subject(s) - mesenchymal stem cell , biology , angiogenesis , paracrine signalling , matrigel , immunology , stem cell , angiogenin , stromal cell , vascular endothelial growth factor , cancer research , microbiology and biotechnology , biochemistry , receptor , vegf receptors
Mesenchymal stromal/stem cells (MSCs) have been developed as a promising source for cell‐based therapies of ischemic disease. However, there are some hurdles in their clinical application such as poor cell engraftment and inconsistent stem cell potency. In this study, we sought to find biomarkers for predicting potency of MSCs for proangiogenic therapy to improve their beneficial effects. Large variations were observed in proangiogenic factor secretion profiles of conditioned media derived from nine different donor‐derived Wharton's jelly (WJ)‐derived MSCs and 8 factors among 55 angiogenesis‐related factors were secreted at considerable levels. Two distinct WJ‐MSCs that had the lowest or the highest secretion of these eight factors showed corresponding proangiogenic activities in in vitro angiogenesis assays. When four additional different donor‐derived WJ‐MSCs were further examined, proangiogenic activities in migration and tube formation of endothelial cells and in in vivo Matrigel plug assay were highly consistent with secretion levels of four major factors (angiogenin, interleukin‐8, monocyte chemoattractant protein‐1, and vascular endothelial growth factor). Such correlation was also observed in vascular regenerative effect in a mouse hind limb ischemia model. Blocking of these four factors by neutralizing antibodies or knockdown of them by siRNA treatment resulted in significant inhibition of proangiogenic activities of not only WJ‐MSCs, but also bone marrow‐derived MSCs. These results suggest that these four factors may represent efficient biomarkers for predicting vascular regenerative efficacy of MSCs. Stem Cells 2019;37:77–88