Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats.
Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats.
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DOI：
10.2337/db08-0031
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发表时间：
2008-11
期刊：
影响因子：
7.7
通讯作者：
Nakamura, Jiro
中科院分区：
文献类型：
--
作者：
Shibata, Taiga;Naruse, Keiko;Kamiya, Hideki;Kozakae, Mika;Kondo, Masaki;Yasuda, Yutaka;Nakamura, Nobuhisa;Ota, Kimiko;Tosaki, Takahiro;Matsuki, Takashi;Nakashima, Eitaro;Hamada, Yoji;Oiso, Yutaka;Nakamura, Jiro
骨髓间充质干细胞（MSC）已被报道分泌各种细胞因子，表现出血管生成和神经支持作用。本研究旨在探讨骨髓间充质干细胞移植对糖尿病性多发性神经病（DPN）大鼠的影响。研究设计和方法：从成年大鼠骨髓中分离出MSC，并通过单侧肌肉注射将其移植到链脲佐菌素（STZ）诱导的糖尿病大鼠或年龄匹配的正常大鼠的后肢骨骼肌中。移植4周后，检测移植部位血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）的含量、电流感觉阈值、神经传导速度（NCV）、坐骨神经血流量（SNBF）、比目鱼肌毛细血管数与肌纤维数的比值、腓肠神经形态计量学。注射MSC的糖尿病大鼠大腿肌肉中VEGF和bFGF mRNA的表达显著增加。此外，证实了MSC与VEGF和bFGF在移植部位的共定位。STZ诱导的糖尿病大鼠表现出痛觉减退、延迟的NCV、SNBF减少和比目鱼肌毛细血管数与肌纤维比率降低，这些都被MSC移植所改善。腓肠神经形态测量显示STZ诱导的糖尿病大鼠轴突环减少，MSC移植使其正常化。结论：这些结果表明，MSC移植可以通过MSC分泌的生长因子的旁分泌作用对DPN产生治疗作用。
OBJECTIVE—Mesenchymal stem cells (MSCs) have been reported to secrete various cytokines that exhibit angiogenic and neurosupportive effects. This study was conducted to investigate the effects of MSC transplantation on diabetic polyneuropathy (DPN) in rats. RESEARCH DESIGN AND METHODS—MSCs were isolated from bone marrow of adult rats and transplanted into hind limb skeletal muscles of rats with an 8-week duration of streptozotocin (STZ)-induced diabetes or age-matched normal rats by unilateral intramuscular injection. Four weeks after transplantation, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) productions in transplanted sites, current perception threshold, nerve conduction velocity (NCV), sciatic nerve blood flow (SNBF), capillary number–to–muscle fiber ratio in soleus muscles, and sural nerve morphometry were evaluated. RESULTS—VEGF and bFGF mRNA expression were significantly increased in MSC-injected thigh muscles of STZ-induced diabetic rats. Furthermore, colocalization of MSCs with VEGF and bFGF in the transplanted sites was confirmed. STZ-induced diabetic rats showed hypoalgesia, delayed NCV, decreased SNBF, and decreased capillary number–to–muscle fiber ratio in soleus muscles, which were all ameliorated by MSC transplantation. Sural nerve morphometry showed decreased axonal circularity in STZ-induced diabetic rats, which was normalized by MSC transplantation. CONCLUSIONS—These results suggest that MSC transplantation could have therapeutic effects on DPN through paracrine actions of growth factors secreted by MSCs.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
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影响因子：
8.2
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Lachapelle, K
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ROBERTSON, S
影响因子：
7.7
作者：
Hotta, N;Koh, N;Sakamoto, N
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