Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes.
Therapeutic efficacy of bone marrow-derived mononuclear cells in diabetic polyneuropathy is impaired with aging or diabetes.
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DOI：
10.1111/jdi.12272
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发表时间：
2015-03
影响因子：
3.2
通讯作者：
Nakamura J
中科院分区：
文献类型：
--
作者：
Kondo M;Kamiya H;Himeno T;Naruse K;Nakashima E;Watarai A;Shibata T;Tosaki T;Kato J;Okawa T;Hamada Y;Isobe K;Oiso Y;Nakamura J
最近的研究表明，细胞移植疗法，如内皮前体细胞、骨髓源性单个核细胞(BM-MNCs)和间充质干细胞，通过改善糖尿病大鼠受损的神经血流，对糖尿病多神经病变具有有效的治疗作用。在这里，我们使用来自成年(16周)糖尿病(AD)、成年非糖尿病(AN)或年轻(8周)非糖尿病(YN)大鼠的BM-MNCs，研究了BM-MNCs移植治疗糖尿病多神经病的效果。糖尿病病程8周后分离AD和AN的BM-MNC。用流式细胞术分析细胞表面标志和多种细胞因子的逆转录-聚合酶链式反应对BM-MNCs进行鉴定。后肢肌肉注射BM-MNCs或生理盐水。4周后检测大鼠足底温度、神经传导速度、坐骨神经血流量及毛细血管/肌纤维比值。与AN或YN相比，AD患者骨髓间充质干细胞中CD29+/CD90+细胞数量减少，BM-MNC中碱性成纤维细胞生长因子和神经生长因子的转录表达减少。YN来源的BM-MNCs能显著改善8周糖尿病大鼠的热感觉障碍、坐骨神经血流量下降和神经传导速度延迟，而AD和AN大鼠的BM-MNCs在这些功能测试中没有显示出任何有益的作用。这些结果表明，BM-MNCs的细胞因子产生能力和间充质干细胞数量会因糖尿病的衰老和代谢变化而改变，这些差异可以解释糖尿病多神经病变患者与青年患者或糖尿病患者与非糖尿病患者BM-MNCs治疗效果差异的原因。
Recent studies have shown that cell transplantation therapies, such as endothelial precursor cells, bone marrow-derived mononuclear cells (BM-MNCs) and mesenchymal stem cells, are effective on diabetic polyneuropathy through ameliorating impaired nerve blood flow in diabetic rats. Here, we investigated the effects of BM-MNCs transplantation in diabetic polyneuropathy using BM-MNCs derived from adult (16-week-old) diabetic (AD), adult non-diabetic (AN) or young (8-week-old) non-diabetic (YN) rats. BM-MNCs of AD and AN were isolated after an 8-week diabetes duration. The BM-MNCs were characterized using flow cytometry analysis of cell surface markers and reverse transcription polymerase chain reaction of several cytokines. BM-MNCs or saline were injected into hind limb muscles. Four weeks later, the thermal plantar test, nerve conduction velocity, blood flow of the sciatic nerve and capillary-to-muscle fiber ratio were evaluated. The number of CD29+/CD90+ cells that host mesenchymal stem cells in BM-MNCs decreased in AD compared with AN or YN, and transcript expressions of basic fibroblast growth factor and nerve growth factor in BM-MNCs decreased in AD compared with AN or YN. Impaired thermal sensation, decreased blood flow of the sciatic nerve and delayed nerve conduction velocity in 8-week-diabetic rats were significantly ameliorated by BM-MNCs derived from YN, whereas BM-MNCs from AD or AN rats did not show any beneficial effect in these functional tests. These results show that cytokine production abilities and the mesenchymal stem cell population of BM-MNCs would be modified by aging and metabolic changes in diabetes, and that these differences could explain the disparity of the therapeutic efficacy of BM-MNCs between young and adult or diabetic and non-diabetic patients in diabetic polyneuropathy.
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影响因子：
8
作者：
Malik, R. A.;Veves, A.;Lauria, G.
通讯作者：
Lauria, G.
影响因子：
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Murakami, Masahiro;Nguyen, Loc T.;Simons, Michael
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Simons, Michael
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Yoon, Young-sup
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Desouza CV;Hamel FG;Bidasee K;O'Connell K
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O'Connell K
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Bakondi, Benjamin;Shimada, Issei S.;Spees, Jeffrey L.
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Spees, Jeffrey L.