Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice.

Angioblast Derived from ES Cells Construct Blood Vessels and Ameliorate Diabetic Polyneuropathy in Mice.
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DOI:
10.1155/2015/257230
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发表时间:
2015
影响因子:
4.3
通讯作者:
Nakamura J
Nakamura J
中科院分区:
医学3区
文献类型:
--
作者:
Himeno T;Kamiya H;Naruse K;Cheng Z;Ito S;Shibata T;Kondo M;Kato J;Okawa T;Fujiya A;Suzuki H;Kito T;Hamada Y;Oiso Y;Isobe K;Nakamura J

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背景虽然已经进行了许多关于糖尿病性多发性神经病的病理累及的报告,但是尚未建立糖尿病性多发性神经病的普遍有效的治疗。最近,再生医学研究糖尿病多发性神经病使用体干/祖细胞已被报道。然而,这些细胞移植的有效性受到限制,因为它们的功能和数量的糖尿病对象的损害。在这里,我们研究了使用来自小鼠胚胎干细胞的成血管细胞样细胞治疗糖尿病多发性神经病的疗效。方法和结果。从小鼠胚胎干细胞中获得成血管细胞样细胞,这些细胞的移植改善了糖尿病多发性神经病的几种生理损伤:痛觉减退,神经传导速度延迟,坐骨神经和足底皮肤的血流量减少。此外,在病理学上,移植后肢骨骼肌中毛细血管数与肌纤维的比率增加,移植足底皮肤中表皮内神经纤维密度改善。移植的细胞保持其活力,并在注射部位周围分化为内皮细胞和平滑肌细胞。此外,几种移植细胞与受体细胞构建了嵌合血管。结论.这些结果表明,胚胎干细胞诱导的成血管细胞样细胞移植似乎是糖尿病多发性神经病的一种新的治疗策略。
Background. Although numerous reports addressing pathological involvements of diabetic polyneuropathy have been conducted, a universally effective treatment of diabetic polyneuropathy has not yet been established. Recently, regenerative medicine studies in diabetic polyneuropathy using somatic stem/progenitor cell have been reported. However, the effectiveness of these cell transplantations was restricted because of their functional and numerical impairment in diabetic objects. Here, we investigated the efficacy of treatment for diabetic polyneuropathy using angioblast-like cells derived from mouse embryonic stem cells. Methods and Results. Angioblast-like cells were obtained from mouse embryonic stem cells and transplantation of these cells improved several physiological impairments in diabetic polyneuropathy: hypoalgesia, delayed nerve conduction velocities, and reduced blood flow in sciatic nerve and plantar skin. Furthermore, pathologically, the capillary number to muscle fiber ratios were increased in skeletal muscles of transplanted hindlimbs, and intraepidermal nerve fiber densities were ameliorated in transplanted plantar skin. Transplanted cells maintained their viabilities and differentiated to endothelial cells and smooth muscle cells around the injection sites. Moreover, several transplanted cells constructed chimeric blood vessels with recipient cells. Conclusions. These results suggest that transplantation of angioblast like cells induced from embryonic stem cells appears to be a novel therapeutic strategy for diabetic polyneuropathy.
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