THERAPEUTIC ANGIOGENESIS INDUCED BY AUTOLOGOUS BONE MARROW CELLS IMPLANTATION FOR THE TREATMENT OF ISCHEMIC DISEASES

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Therapeutic angiogenesis can be induced by the implantation of bone marrow mononuclear cells (BM-MNCs), but the best cell fraction in BM-MNCs and the best delivery road for inducing therapeutic angiogenesis kept unclear.At first, we investigated the roles of stem cell fractions in BM-MNCs in this treatment. Stem cells were separated from mature BM-MNCs of mice using the antibody to stem cell receptor (CD117). More than ten-fold higher levels of VEGF were secreted from the CD117^+ cells than from the CD117^- cells (P< 0.001) 14 days after culture. Most of the CD117^- cells died, but the CD117^+ cells grew well and differentiated into endothelial ceils within 14 days of culture. CD117^+ cells (2 x 10^5), CD117^- cells (9.8 x 10^6), and total BM-MNCs (1 x 10^7) were also implanted into the ischemic hindlimbs of mice. The blood perfusion of the ischemic hindlimbs was significantly higher in the CD117^+ cell-implanted mice than in the CD117^- cell-implanted mice (P<0.01), but did not differ significantly from the BM-MNCs cell-implanted mice, 14 days after treatment. These results indicated that CD117^+ stem cells play a key role in the therapeutic angiogenesis induced by bone marrow cell implantation.Then, we investigated the potency of therapeutic angiogenesis inducing by BM-MNCs using different delivery roads in an acute myocardium infarction model in rats. After the ligation of left ascending coronary artery, BM-MNCs (1 x 10^7) were given intramuscularly (IM group) or intravenously (IV group). The survival of BM-MNCs was better in the IM group than the IV group. Furthermore, both the blood flow of infarction area and the cardiac ejection fraction were significantly higher in the IM group than the IV group. These results indicated that the angiogenic potency inducing by BM-MNCs implantation was better by local intramuscularly injection than by intravenous delivery.