Mesenchymal Stem Cells from Bone Marrow Enhance Neovascularization and Stromal Cell Proliferation in Rat Ischemic Limb in the Early Phase after Implantation

  • USUI Sayaka
    Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital Department of Anatomy, Showa University School of Medicine
  • ISO Yoshitaka
    Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital Division of Cardiology, Showa University Fujigaoka Rehabilitation Hospital
  • SASAI Masahiro
    Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital Department of Anatomy, Showa University School of Medicine
  • MIZUKAMI Takuya
    Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital Department of Anatomy, Showa University School of Medicine
  • SATO Chisato
    Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital
  • KURATA Masaaki
    Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital
  • UMEZAWA Akihiro
    Department of Reproductive Biology, Center for Regenerative Medicine, National Institute for Child Health and Development
  • SHIODA Seiji
    Department of Anatomy, Showa University School of Medicine
  • SUZUKI Hiroshi
    Division of Cardiology, Department of Internal Medicine, Showa University Fujigaoka Hospital

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Accumulating evidence from animal studies shows that the administration of mesenchymal stem cells (MSCs) from adult bone marrow ameliorates tissue damage after ischemic injury. In the present study we investigated the efficacy of MSC implantation into a hindlimb ischemia model over a short-term period to elucidate the effects conferred within the early phase after treatment. MSCs from rats expressing green fluorescence protein (GFP) were injected into rat ischemic limbs. Laser Doppler perfusion imaging revealed significantly higher blood perfusion recovery in the MSC group than in the control group on days 3 and 7 after the treatment. The capillary/muscle fiber ratio in ischemic muscle was also significantly higher in the MSC group than in the controls in a histological study. In spite of these benefits, we found no evident engraftment of the GFP-positive cells, and instead, the MSC treatment induced a proliferation of resident stromal cells in the perivascular area of the ischemic muscle, some of which produced vascular endothelial growth factor. The present study suggested that MSC therapy promotes neovascularization even in the early phase, both directly through endothelial proliferation and indirectly through activation of the resident stromal cells.

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