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

Abstract : 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 ef˜cacy 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 ˚uorescence protein （GFP） were injected into rat ischemic limbs. Laser Doppler perfusion imaging revealed signi˜cantly higher blood perfu-sion recovery in the MSC group than in the control group on days 3 and 7 after the treatment. The capillary / muscle ˜ber ratio in ischemic muscle was also sig-ni˜cantly higher in the MSC group than in the controls in a histological study. In spite of these bene˜ts, 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 prolif-eration and indirectly through activation of the resident stromal cells.