Low-molecular weight heparin protamine complex augmented the potential of adipose-derived stromal cells to ameliorate limb ischemia
Low-molecular weight heparin protamine complex augmented the potential of adipose-derived stromal cells to ameliorate limb ischemia
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DOI：
10.1016/j.atherosclerosis.2016.04.003
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发表时间：
2016-06-01
期刊：
影响因子：
5.3
通讯作者：
Yoshida, Ken-ichiro
中科院分区：
文献类型：
--
作者：
Kishimoto, Satoko;Inoue, Ken-ichi;Yoshida, Ken-ichiro
背景和目标：肝素/鱼精蛋白微/纳米粒（LH/P-MPs）是近年来发展起来的一种低分子量、可生物降解的脂肪基质细胞（ADSCs）载体。这些颗粒可用于促进血管生成的局部递送干细胞疗法。LH/P-MP结合于ADSC的细胞表面，并促进ADSC的细胞间相互作用和聚集。培养的ADSC/LH/P-MP聚集体保持活力。在这里，我们研究了这些聚集体的能力，以挽救肢体损失的小鼠模型hindlimb ischemia.Methods：单侧后肢缺血诱导成年雄性BALB/c小鼠髂动脉和后肢静脉结扎。对于同种异体移植来自同一近交系的ADSC，我们将单独的ADSC或ADSC/LH/P-MP聚集体或对照培养基（假处理）直接注射到缺血肌肉中。记录缺血肢体血流灌注、血管密度和血管面积。术后第2、7、14天评估缺血性肢体坏死或肢体缺损的程度。结果：与假手术对照组相比，单独应用ADSCs对血液灌注恢复有一定影响，并增加了α-SMA阳性血管的数量。对于每个终点，对ADSC/LH/P-MP聚集体的应答显著大于单独的ADSC。结论：LH/P-MP复合物能增强ADSC促进血管生成和逆转肢体缺血的作用。使用ADSC/LH/P-MP聚集体提供了一种新颖且方便的治疗方法，并可能代表了诱导缺血性疾病中血管生成的有前途的新治疗方法。(C)2016作者由Elsevier爱尔兰有限公司发布。这是CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Background and aims: Heparin/protamine micro/nanoparticles (LH/P-MPs) were recently developed as low-molecular weight, biodegradable carriers for adipose-derived stromal cells (ADSCs). These particles can be used for a locally delivered stem cell therapy that promotes angiogenesis. LH/P-MPs bind to the cell surface of ADSCs and promote cell-to-cell interaction and aggregation of ADSCs. Cultured ADSC/LH/P-MP aggregates remain viable. Here, we examined the ability of these aggregates to rescue limb loss in a mouse model of hindlimb ischemia.Methods: Unilateral hindlimb ischemia was induced in adult male BALB/c mice by ligation of the iliac artery and hindlimb vein. For allotransplantation of ADSCs from the same inbred strain, we injected ADSC alone or ADSC/LH/P-MP aggregates or control medium (sham-treated) directly into the ischemic muscles. Ischemic limb blood perfusion, vessel density, and vessel area were recorded. The extent of ischemic limb necrosis or limb loss was assessed on postoperative days 2, 7, and 14.Results: Compared with the sham-treatment control, treatment with ADSCs alone showed modest effects on blood perfusion recovery and increased the number of alpha-SMA-positive vessels. Response to ADSC/LH/P-MP aggregates was significantly greater than ADSCs alone for every endpoint. ADSC/LH/P-MP aggregates more effectively prevented the loss of ischemic hindlimbs than ADSCs alone or the sham-treatment.Conclusion: The LH/P-MPs augmented the effects of ADSCs on angiogenesis and reversal of limb ischemia. Use of ADSC/LH/P-MP aggregates offers a novel and convenient treatment method and potentially represents a promising new therapeutic approach to inducing angiogenesis in ischemic diseases. (C) 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).