Adequate Selection of a Therapeutic Site Enables Efficient Development of Collateral Vessels in Angiogenic Treatment With Bone Marrow Mononuclear Cells.
Adequate Selection of a Therapeutic Site Enables Efficient Development of Collateral Vessels in Angiogenic Treatment With Bone Marrow Mononuclear Cells.
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DOI：
10.1161/jaha.115.002287
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发表时间：
2015-09-14
影响因子：
5.4
通讯作者：
Watanabe T
中科院分区：
文献类型：
--
作者：
Nemoto M;Koyama H;Nishiyama A;Shigematsu K;Miyata T;Watanabe T
诱导血管生成机制以促进侧支血管的发育被认为有希望用于治疗外周动脉疾病。侧支血管通常从预先存在的小动脉连接处发展而来，绕过患病的动脉。我们推测，诱导血管生成机制应针对这样的小动脉连接，以实现有效的侧支发展。本研究的目的是通过自体骨髓单个核细胞移植到慢性肢体缺血的家兔模型中来验证这一假设。切除雄性家兔左股动脉，诱导肢体缺血。在该模型中，左侧尾骨股肌中的小动脉连接倾向于发展成侧支血管，尽管这种转化不足以缓解肢体缺血。与此相反，在紧密定位的收肌小动脉连接不容易发展成侧支血管。在缺血开始后21天，选择性地将足够数量的自体单核细胞注射到左侧尾骨股肌（尾骨组）或左侧内收肌（内收肌组）。在注射后第28天，对小腿血压比、左髂内动脉血流和血管造影评分的评估显示，尾肌组的侧支循环发展和肢体缺血改善明显优于内收肌组。第14天尾骨股肌的形态测量分析显示了类似的结果。在兔肢体缺血模型中，将单核细胞特异性递送至尾骨股肌而不是内收肌有效地改善了侧支循环，并表明适当的部位选择可以促进治疗性血管生成。
Induction of angiogenic mechanisms to promote development of collateral vessels is considered promising for the treatment of peripheral arterial diseases. Collateral vessels generally develop from preexisting arteriolar connections, bypassing the diseased artery. We speculated that induction of angiogenic mechanisms should be directed to such arteriolar connections to achieve efficient collateral development. The aim of this study was to verify this hypothesis using autologous transplantation of bone marrow mononuclear cells in the rabbit model of chronic limb ischemia. The left femoral artery was excised to induce limb ischemia in male rabbits. In this model, arteriolar connections in the left coccygeofemoral muscle tend to develop into collateral vessels, although this transformation is insufficient to alleviate the limb ischemia. In contrast, arteriolar connections in the closely located adductor muscle do not readily develop into collateral vessels. At 21 days after ischemia initiation, a sufficient number of automononuclear cells were selectively injected in the left coccygeofemoral muscle (coccygeo group) or left adductor muscle (adductor group). Evaluation of calf blood pressure ratios, blood flow in the left internal iliac artery, and angiographic scores at day 28 after injection revealed that collateral development and improvement of limb ischemia were significantly more efficient in the coccygeo group than in the adductor group. Morphometric analysis of the coccygeofemoral muscle at day 14 showed similar results. Specific delivery of mononuclear cells to the coccygeofemoral but not the adductor muscle effectively improves collateral circulation in the rabbit model of limb ischemia and suggests that adequate site selection can facilitate therapeutic angiogenesis.