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

被引:13
作者
Himeno, Tatsuhito [1 ,2 ]
Kamiya, Hideki [3 ,4 ]
Naruse, Keiko [5 ]
Cheng, Zhao [2 ]
Ito, Sachiko [2 ]
Shibata, Taiga [1 ]
Kondo, Masaki [1 ,2 ]
Kato, Jiro [1 ]
Okawa, Tetsuji [1 ,2 ]
Fujiya, Atsushi [1 ,6 ]
Suzuki, Hirohiko [2 ]
Kito, Tetsutaro [2 ]
Hamada, Yoji [6 ]
Oiso, Yutaka [1 ]
Isobe, Kenichi [2 ]
Nakamura, Jiro [1 ,4 ]
机构
[1] Nagoya Univ, Grad Sch Med, Dept Endocrinol & Diabet, Showa Ku, Nagoya, Aichi 4668550, Japan
[2] Nagoya Univ, Grad Sch Med, Dept Immunol, Showa Ku, Nagoya, Aichi 4668550, Japan
[3] Nagoya Univ, Grad Sch Med, Dept Chron Kidney Dis Initiat, Showa Ku, Nagoya, Aichi 4668550, Japan
[4] Aichi Med Univ, Sch Med, Dept Internal Med, Div Diabet, Nagakute, Aichi 4801195, Japan
[5] Aichi Gakuin Univ, Sch Dent, Dept Internal Med, Chikusa Ku, Nagoya, Aichi 4648650, Japan
[6] Nagoya Univ, Grad Sch Med, Dept Metab Med, Showa Ku, Nagoya, Aichi 4668550, Japan
关键词
ENDOTHELIAL PROGENITOR CELLS; PROTEIN-KINASE-C; NERVE-CONDUCTION-VELOCITY; FIBROBLAST-GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; PERIPHERAL NEUROPATHY; ENDONEURIAL MICROVESSELS; VASCULAR COMPLICATIONS; STROMAL CELLS; HYPERGLYCEMIA;
D O I
10.1155/2015/257230
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页数:17
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