Mesenchymal Stem Cells Differentiate into an Endothelial Phenotype, Reduce Neointimal Formation, and Enhance Endothelial Function in a Rat Vein Grafting Model

Abstract

Autologous vein grafts is still commonly used for arterial reconstructive procedures. Their success is limited by the development of neointimal hyperplasia. Clinical and experimental evidence suggest that the bone marrow derived mesenchymal stem cells (MSCs) participate in the neovascularization. The current study used a direct approach to test the hypothesis that, after vein grafting in a rat model, MSCs have potential effects on reendothelialization and neointimal formation. MSCs were isolated by bone marrow cell adherence. Autologously interpositioning left external jugular vein (LEJV) to left common carotid artery-induced vein grafting model of r at w as utilized. Vascular lesion formation after transplantation of MSCs labeled with 4',6-diamidino-2-phenylindole (DAPI) was investigated. Two weeks after implantation, immunofluorescence studies revealed that engrafted cells acquired an endothelial phenotype, and some expressed endothelial nitric oxide synthase (eNOS). Furthermore, proliferation of cells and neointimal formation decreased significantly after MSC implantation. Real-time reverse transcription-PCR and western blotting analysis showed a rise of eNOS expression in the MSC group compared with the vein grafting group. Therefore, engrafted MSCs appeared to differentiate into endothelial cells, diminish the neointima formation and contribute to the improvement on endothelial function, which indicates that MSCs may exert an important function as repair mechanism in vascular injury after vein grafting.

Mesenchymal Stem Cells: A Good Candidate for Restenosis Therapy?

“…The above illustrated data concerning the positive effect played by allogenic murine MSCs in a model of carotid arteriotomy [104] are in agreement with similar studies conducted in a model of rat vein-to-artery graft, showing that injected MSCs are able to reduce (re)stenosis by reducing cell proliferation, reducing neointima formation and by enhancing endothelial function, revealed by their differentiation into ECs and by increased expression of eNOS two weeks after implantation [127].…”

Rehmannia glutinosa oligosaccharide induces differentiation of bone marrow mesenchymal stem cells into cardiomyocyte-like cells

“…Bone marrow mesenchymal stem cells (MSCs) have been commonly used as donor stem cells for transplantation as they can differentiate into diverse cell types, including cardiomyocyte-like cells and vascular endothelial cells (Antonitsis et al, 2008;Yue et al, 2008). 5-Azacytidine (5-aza) is often used to induce differentiation of MSCs into myocardial cells; however, 5-aza is associated with various adverse effects as an antitumor drug (Borodovsky et al, 2013).…”

Endothelial-like cells differentiated from mesenchymal stem cells attenuate neointimal hyperplasia after vascular injury

“…The ability of MSCs to differentiate into either endothelial cells or VSMCs in vitro has been previously well characterized and documented (18–21). In comparison, differentiation to endothelial cells or vascular muscle cells in vivo subsequent to arterial injury remains unclear.…”