Hypoxic mesenchymal stem cells engraft and ameliorate limb ischaemia in allogeneic recipients
Hypoxic mesenchymal stem cells engraft and ameliorate limb ischaemia in allogeneic recipients
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DOI：
10.1093/cvr/cvt250
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发表时间：
2014-02-01
影响因子：
10.8
通讯作者：
Hung, Shih-Chieh
中科院分区：
文献类型：
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作者：
Huang, Wei-Hua;Chen, Hen-Li;Hung, Shih-Chieh
直接向缺血组织局部注射干细胞或内皮祖细胞仍然是治疗动脉闭塞的一种选择。骨髓间充质干细胞(MSCs)是治疗肢体缺血的一种很有前途的自体细胞来源。然而，将间充质干细胞应用于异基因移植的方法仍有待开发。本研究的目的是评价在不同环境下培养的骨髓间充质干细胞在改善异基因移植受者肢体缺血方面的治疗潜力。我们还证明了低氧的MSCs在体内移植时，通过降低自然杀伤(NK)细胞毒性和减少宿主来源的NK细胞的积聚，提高了移植到同种异体受体的能力。这些同种异体低氧骨髓间充质干细胞分化为CD31内皮细胞、平滑肌肌动蛋白(SMA)和结蛋白肌细胞，从而促进血管生成，恢复肌肉结构。此外，抗NK抗体联合常氧MSCs的应用可促进肢体缺血的同种异体移植受者的血管生成，防止截肢。这些结果有力地表明，缺氧的MSCs具有固有的免疫应答，可以作为通用的供体细胞用于治疗心血管疾病。
Local injection of stem cells or endothelial progenitors directly into the ischaemic tissue remains an option for the management of arterial occlusion. Bone marrow-derived mesenchymal stem cells (MSCs) represent a promising alternative autologous cell source for ischaemic limb cell therapy. However, methods for applying MSCs in allogeneic transplantation remain to be developed. The purpose of this study was to evaluate the therapeutic potential of MSCs cultured under a different environment in ameliorating limb ischaemia in allogeneic recipients.Here, we demonstrated that hypoxic MSCs from B6 mice ameliorate limb ischaemia of Balb/c mice compared with normoxic MSCs. We also demonstrated that hypoxic MSCs have an increased ability to engraft in allogeneic recipients by reducing natural killer (NK) cytotoxicity and decrease the accumulation of host-derived NK cells when transplanted in vivo. These allogeneic hypoxic MSCs gave rise to CD31 endothelial cells and -smooth muscle actin (SMA) and desmin muscle cells, thereby enhancing angiogenesis and restoring muscle structure. Moreover, application of anti-NK antibodies together with normoxic MSCs enhanced angiogenesis and prevented limb amputation in allogeneic recipients with limb ischaemia.These results strongly suggest that hypoxic MSCs are intrinsically immunoprivileged and can serve as a universal donor cell for treating cardiovascular diseases.