Mesenchymal stem cells differentiate into an endothelial phenotype, reduce neointimal formation, and enhance endothelial function in a rat vein grafting model

Stem Cells Dev. 2008 Aug;17(4):785-93. doi: 10.1089/scd.2007.0243.

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.

MeSH terms

  • Animals
  • Carotid Artery Injuries / enzymology
  • Carotid Artery Injuries / pathology
  • Carotid Artery Injuries / surgery
  • Carotid Artery, Common / enzymology
  • Carotid Artery, Common / pathology
  • Carotid Artery, Common / surgery
  • Cell Differentiation*
  • Disease Models, Animal
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / enzymology*
  • Mesenchymal Stem Cells / pathology
  • Nitric Oxide Synthase Type II / biosynthesis
  • Nitric Oxide Synthase Type III
  • Rats
  • Rats, Wistar
  • Time Factors
  • Transplantation, Autologous
  • Tunica Intima / enzymology*
  • Tunica Intima / pathology
  • Veins / enzymology
  • Veins / pathology
  • Veins / transplantation*

Substances

  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat