Mesenchymal Stem Cell-Like Cells Derived from Mouse Induced Pluripotent Stem Cells Ameliorate Diabetic Polyneuropathy in Mice

被引：36

作者：

Himeno, Tatsuhito ^{[1
,2
]}

Kamiya, Hideki ^{[1
,3
,4
]}

Naruse, Keiko ^{[5
]}

Cheng, Zhao ^{[2
]}

Ito, Sachiko ^{[2
]}

Kondo, Masaki ^{[2
]}

Okawa, Tetsuji ^{[1
,2
]}

Fujiya, Atsushi ^{[1
,6
]}

Kato, Jiro ^{[1
]}

Suzuki, Hirohiko ^{[2
]}

Kito, Tetsutaro ^{[2
]}

Hamada, Yoji ^{[6
]}

Oiso, Yutaka ^{[1
]}

Isobe, Kenichi ^{[2
]}

Nakamura, Jiro ^{[3
]}

机构：

[1] Nagoya Univ, Grad Sch Med, Dept Endocrinol & Diabet, Nagoya, Aichi 4668560, Japan

[2] Nagoya Univ, Grad Sch Med, Dept Immunol, Nagoya, Aichi 4668560, Japan

[3] Aichi Med Univ, Sch Med, Dept Internal Med, Div Diabet, Nagakute, Aichi 4801195, Japan

[4] Nagoya Univ, Grad Sch Med, Dept CKD Initiat, Nagoya, Aichi 4668560, Japan

[5] Aichi Gakuin Univ, Sch Dent, Dept Internal Med, Nagoya, Aichi 4648651, Japan

[6] Nagoya Univ, Grad Sch Med, Dept Metab Med, Nagoya, Aichi 4668560, Japan

来源：

BIOMED RESEARCH INTERNATIONAL | 2013年 / 2013卷

关键词：

PROTEIN-KINASE-C; NERVE-CONDUCTION-VELOCITY; ENDONEURIAL BLOOD-FLOW; ENDOTHELIAL-CELLS; NEUROPATHY; RATS; PATHOGENESIS; ANTIOXIDANT; ACTIVATION; EXPRESSION;

D O I：

10.1155/2013/259187

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Background. Although pathological involvements of diabetic polyneuropathy (DPN) have been reported, no dependable treatment of DPN has been achieved. Recent studies have shown that mesenchymal stem cells (MSCs) ameliorate DPN. Here we demonstrate a differentiation of induced pluripotent stem cells (iPSCs) into MSC-like cells and investigate the therapeutic potential of the MSC-like cell transplantation on DPN. Research Design and Methods. For induction into MSC-like cells, GFP-expressing iPSCs were cultured with retinoic acid, followed by adherent culture for 4 months. The MSC-like cells, characterized with flow cytometry and RT-PCR analyses, were transplanted into muscles of streptozotocin-diabetic mice. Three weeks after the transplantation, neurophysiological functions were evaluated. Results. The MSC-like cells expressed MSC markers and angiogenic/neurotrophic factors. The transplanted cells resided in hindlimb muscles and peripheral nerves, and some transplanted cells expressed S100 beta in the nerves. Impairments of current perception thresholds, nerve conduction velocities, and plantar skin blood flow in the diabetic mice were ameliorated in limbs with the transplanted cells. The capillary number-to-muscle fiber ratios were increased in transplanted hindlimbs of diabetic mice. Conclusions. These results suggest that MSC-like cell transplantation might have therapeutic effects on DPN through secreting angiogenic/neurotrophic factors and differentiation to Schwann cell-like cells.

引用

页数：12

共 42 条

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