Therapeutic angiogenesis by cell transplantation

最近，自体骨髓单个核细胞（BM-MNCs）移植到缺血肢体的治疗性血管生成的有效性和安全性已被报道。我们研究了外周血单个核细胞（PB-MNC）移植是否也将作为BM-MNC移植外周动脉疾病患者的有效性。在5例患者中进行了BM-MNC移植到单侧缺血肢体中，并且在5例患者中进行了BM-MNC和PB-MNC移植到双侧缺血肢体中（BM-MNC移植到严重缺血肢体中，相同数量的PB-MNC移植到对侧缺血较少的肢体中）。PB-MNCs中的CD 34 ^+细胞数量比BM-MNCs中的少100倍，而PB-MNCs在24小时孵育期间分泌大量的血管内皮生长因子（VEGF）。单独移植BM-MNC没有增加血清VEGF水平，而移植BM-MNC和PB-MNC后血清VEGF水平显著增加。移植后两周，BM-MNC移植肢体的踝臂指数和经皮氧分压显著增加，而PB-MNC移植肢体的这些参数没有显著增加。我们证明，BM-MNC的自体移植代表了一种新的和有前途的临床应用策略，旨在使缺血组织再血管化，但PB-MNCs移植治疗效果不明确。

Recently, the effectiveness and safety of therapeutic angiogenesis by transplantation of autologous bone marrow mononuclear cells (BM-MNCs) to ischemic limbs have been reported. We investigated whether transplantation of peripheral blood mononuclear cells (PB-MNCs) would also be as effective as BM-MNC-transplantation in patients with peripheral arterial disease. BM-MNC-transplantation into unilateral ischemic limbs was performed in five patients, and both BM-MNC and PB-MNC-transplantation into bilateral ischemic limbs (BM-MNCs into severe ischemic limbs and the same number of PB-MNCs into contralateral less ischemic limbs) were performed in five patients. The number of CD34^+ cells in PB-MNCs was 〜100-fold less than that in BM-MNCs, while PB-MNCs secreted substantial amounts of vascular endothelial growth factor (VEGF) during a 24-hour incubation. There was no increase in the serum VEGF levels by BM-MNC-transplantation alone, while there was a significant increase in the serum VEGF levels after transplantation of both BM-MNCs and PB-MNCs. Two weeks after transplantation, the ankle-brachial index and transcutaneous oxygen pressure were significantly increased in BM-MNC-transplanted limbs, while there were no significant increases in these parameters in PB-MNC-transplanted limbs.We demonstrate that autologous transplantation of BM-MNCs represents a new and promising strategy for clinical application designed to revascularize ischemic tissues, but there were no definite therapeutic effects of transplantation of PB-MNCs.