Therapeutic vasculogenesis using bone marrow mononuclear cells for painful diabetic neuropathy

使用骨髓单核细胞治疗疼痛性糖尿病神经病变的血管生成

• 批准号: 18613019
• 负责人: NARUSE Keiko
• 金额: $ 2.49万
• 依托单位: Aichi Gakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18613019/
• 关键词: Diabetic neuropathy; Therapeutic vasculogenesis; Regenerative medicine; Bone marrow mononuclear cell

Diabetic neuropathy is characterized by altered sensory excitability. The positive symptoms, including hyperalgesia, are often present in the early stage of diabetes. Since bone marrow is a rich source of not only vascular progenitor cells but also cytokines, we have examined whether the transplantation of bone marrow-derived MNCs into hindlimb muscles improves hyperalgesia observed in the early stage of STZ-induced diabetic rats.Diabetes was induced by an intraperitoneal injection of STZ (60mg/Kg) into 6 week-old Sprague-Dawley rats. 2 weeks later, MNCs isolated from bone marrow or saline were injected into unilateral hindlimb skeletal muscles of diabetic rats. Behavioral nociceptive responses were measured every 2 or 3 days using von Frey hair. Two weeks after the injection of MNCs, sciatic nerve conduction velocity (NCV), and sciatic nerve blood flow (SNBF) were measured. mRNA expression of several cytokines in bone marrow-derived MNCs were examined using real time PCR. The frequenc … More y of paw withdrawal started to increase after STZ administration. The transplantation of MNCs significantly decreased the frequency of paw withdrawal in MNCs-injected side of diabetic rats compared with those in saline-injected side of diabetic rats. The effects of MNCs transplantation on hyperalgesia was observed from 3 days after MNCs transplantation until observation periods. Electrophysiological studies revealed that the trasnplantation of MNCs significantly ameliorated the impaired-NCV and SNBF in MNCs-injected side of diabetic rats compared with those in saline-injected side of diabetic rats. The mRNA expressions of the basic fibroblast growth factor and vascular endothelial growth factor were observed in MNCs.These results indicate that bone marrow-derived MNCs is useful for not only therapeutic vasculogenesis but also a source of cytokines, suggesting that the transplantation of bone marrow-derived MNCs may be an effective therapy for hyperalgesia in the early stage of diabetes. Less

糖尿病神经病变的特征在于感觉兴奋性改变。阳性症状，包括痛觉过敏，往往出现在糖尿病的早期阶段。由于骨髓不仅是血管祖细胞的丰富来源，而且也是细胞因子，我们已经研究了骨髓来源的MNCs移植到后肢肌肉是否改善在早期观察到的STZ诱导的糖尿病rates.Diabetes大鼠腹腔注射STZ（60 mg/Kg）到6周龄的Sprague-Dawley大鼠的痛觉过敏。2周后，将从骨髓或生理盐水中分离的MNCs注射到糖尿病大鼠的单侧后肢骨骼肌中。每2或3天使用von Frey毛发测量行为伤害性反应。两周后测定坐骨神经传导速度（NCV）和坐骨神经血流量（SNBF）。采用真实的时间PCR检测骨髓来源的MNCs中几种细胞因子的mRNA表达。频率 ...更多信息 STZ给药后，缩爪的y开始增加。与盐水注射侧相比，MNCs移植可显著降低糖尿病大鼠MNCs注射侧的缩足次数。从移植后第3天起至观察期观察MNCs移植对痛觉过敏的影响。神经电生理研究显示，与生理盐水注射侧相比，移植MNCs后糖尿病大鼠MNCs注射侧的神经传导速度和SNBF明显改善。结果表明，骨髓来源的MNCs不仅具有治疗性血管生成作用，而且是细胞因子的来源，骨髓来源的MNCs移植可能是治疗糖尿病早期痛觉过敏的有效方法。少

项目成果

Transplantation of bone marrow-derived mesenchymal stem cells improves diabetic polyneuropathy in rats.

• DOI: 10.2337/db08-0031
• 发表时间: 2008-11
• 期刊: DIABETES
• 影响因子: 7.7
• 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
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• 作者: Hideki Ishii;et al.;成瀬 桂子;Nobuhisa Nakamura;Tiga Shibata;柴田 大河;渡会 敦子;中村 信久;中村 二郎
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• 发表时间: 2007
• 作者: Takashi kawamura;et al.;佐藤 純;舟久保 恵美;佐藤 純;成瀬 桂子;柴田 大河;申 正樹;申 正樹;Jiro Nakamura;Jiro Nakamura;成瀬 桂子
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关于 1 型糖尿病 BB/Wor-rats 的终末轴突变性

• 发表时间: 2007
• 作者: Takashi kawamura;et al.;佐藤 純;舟久保 恵美;佐藤 純;成瀬 桂子;柴田 大河;申 正樹;申 正樹;Jiro Nakamura;Jiro Nakamura;成瀬 桂子;佐藤 純;Nobuhisa Nakamura;Eitaro Nakashima;Taiga Shibata;Eitaro Nakashima;Nobuhisa Nakamura;戸崎 貴博;柴田 大河;渡会 敦子;神谷 英紀
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多元醇最新糖尿病学-基础和临床-

• 发表时间: 2006
• 作者: Takashi kawamura;et al.;佐藤 純;舟久保 恵美;佐藤 純;成瀬 桂子;柴田 大河;申 正樹;申 正樹;Jiro Nakamura;Jiro Nakamura;成瀬 桂子;佐藤 純;Nobuhisa Nakamura;Eitaro Nakashima;Taiga Shibata;Eitaro Nakashima;Nobuhisa Nakamura;戸崎 貴博;柴田 大河;渡会 敦子;神谷 英紀;戸崎 貴博;中村 信久;Jiro Nakamura;Jiro Nakamura;高橋 賢;申 正樹;Keiko Naruse;Keiko Naruse;Eitaro Nakashima;Mika Nakae;Kimiko Ota;Yasuko Kobayashi;Nachi Kimura;Eitaro Nakashima;Mika Nakae;Kimiko Ota;Yasuko Kobayashi;Nachi Kimura;中村 二郎;成瀬 桂子;佐藤 純;成瀬 桂子;中村 二郎;中村 二郎
• 通讯作者: 中村 二郎