Therapeutic Angiogenesis with Autologous Mesenchymal Stem Cell in Patients with Peripheral Artery Diseases: Mesenchymal Stem Cell Storing System

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Mesenchymal stem cells (MSCs) can differentiate into osteoblasts, nerve cells, skeletal muscle cells, and vascular endothelial cells in vivo and in vitro. It has been reported that MSC implantation induces active angiogenesis in ischemic limbs. We evaluated the effect of MSC implantation on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSC were implanted or saline was injected as a control group. LBF was measured using an electromagnetic flowmeter. A total of 10^6MSCs were implanted into each ischemic limb. Histological sections of ischemic muscle showed that capillary index was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of N^G-nitro-L-arginine, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar. MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.It is clear that BM-MNC implantation is useful for patients with severe limb ischemia. However, patients were subjected by general anesthesia during BM-MNC aspiration. In the present study, we established the autologous MSC culture method. We are making a plan to store cultured MSC and to perform the autologous MSC implantation in patients with limb ischemia.