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Publication : Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis.

First Author  Redgrave RE Year  2017
Journal  Stem Cell Reports Volume  8
Issue  5 Pages  1287-1298
PubMed ID  28494939 Mgi Jnum  J:254979
Mgi Id  MGI:6113744 Doi  10.1016/j.stemcr.2017.04.015
Citation  Redgrave RE, et al. (2017) Cardiosphere-Derived Cells Require Endoglin for Paracrine-Mediated Angiogenesis. Stem Cell Reports 8(5):1287-1298
abstractText  Clinical trials of stem cell therapy to treat ischemic heart disease primarily use heterogeneous stem cell populations. Small benefits occur via paracrine mechanisms that include stimulating angiogenesis, and increased understanding of these mechanisms would help to improve patient outcomes. Cardiosphere-derived-cells (CDCs) are an example of these heterogeneous stem cell populations, cultured from cardiac tissue. CDCs express endoglin, a co-receptor that binds specific transforming growth factor beta (TGFbeta) family ligands, including bone morphogenetic protein 9 (BMP9). In endothelial cells endoglin regulates angiogenic responses, and we therefore hypothesized that endoglin is required to promote the paracrine pro-angiogenic properties of CDCs. Cre/LoxP technology was used to genetically manipulate endoglin expression in CDCs, and we found that the pro-angiogenic properties of the CDC secretome are endoglin dependent both in vitro and in vivo. Importantly, BMP9 pre-treatment of endoglin-depleted CDCs restores their pro-angiogenic paracrine properties. As BMP9 signaling is normally required to maintain endoglin expression, we propose that media containing BMP9 could be critical for therapeutic CDC preparation.
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