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Human mesenchymal stem cells support capillary‐like structures in a 3D model of in vitro angiogenesis
Author(s) -
Hall Sean Ralph Robert,
Chen Zhilin,
Ward Christopher,
Melo Luis
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a145
Subject(s) - mesenchymal stem cell , pericyte , progenitor cell , microbiology and biotechnology , desmin , angiogenesis , stem cell , population , myofibroblast , endothelial stem cell , neovascularization , biology , chemistry , pathology , immunology , in vitro , cancer research , medicine , immunohistochemistry , fibrosis , vimentin , biochemistry , environmental health
Adult human mesenchymal stem cells (hMSCs) are a rare population of fibroblast‐like cells found within the bone marrow stroma. These cells have a high degree of plasticity and are able to differentiate into a wide variety of cell types. In the current study, we investigated whether hMSCs represent a novel vascular progenitor cell that may be involved in neovessel formation. hMSCs and endothelial progenitor cells (EPCs) were cultured alone or together in Matrigel TM . Tube formation was visualized by fluorescence using an inverted microscope. In separate experiments, hMSCs were treated with TGF‐β1, (2.5ng/ml) or PDGF‐BB, (10ng/ml) for 4 days and stained for pericyte markers α‐smooth muscle actin (α‐SMA), desmin and PDGF receptor‐beta (PDGFR‐β). When cultured alone on Matrigel TM , EPCs and hMSCs formed tube‐like structures reminiscent of primitive vessels. Co‐culture of EPCs and hMSCs led to the formation of multicellular vascular tubes. hMSCs migrated towards and invested around EPC‐derived tubes demonstrating a cell‐cell interaction, likely mediated by paracrine effectors. Treatment of hMSCs with TGF‐β1 induced differentiation towards a pericyte phenotype, demonstrated by positive staining for α‐SMA and desmin. We conclude that hMSCs interact with EPCs to form primitive vessels. Moreover, treatment of hMSCs with TGF‐β1 promotes the expression of pericytes markers that support growing vessels. Therefore, hMSC is a vascular progenitor cell, which may serve as a cell substrate for efficient and sustainable therapeutic neovascularization. Supported by a Merck Frosst Pharmacology Fellowship to SRR Hall and CIHR grants to L Melo and C Ward .