Transplantation of bone marrow-derived mononuclear cells improves mechanical hyperalgesia, cold allodynia and nerve function in diabetic neuropathy.

Transplantation of bone marrow-derived mononuclear cells improves mechanical hyperalgesia, cold allodynia and nerve function in diabetic neuropathy.
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DOI:
10.1371/journal.pone.0027458
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Nakamura J
Nakamura J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Naruse K;Sato J;Funakubo M;Hata M;Nakamura N;Kobayashi Y;Kamiya H;Shibata T;Kondo M;Himeno T;Matsubara T;Oiso Y;Nakamura J

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缓解疼痛性糖尿病神经病变是一个重要的临床问题。我们以前已经证明,移植培养的内皮祖细胞或间充质干细胞改善糖尿病大鼠神经病变。在这项研究中,我们调查是否移植新鲜分离的骨髓来源的单核细胞(BM-MNCs)减轻神经病理性疼痛的早期阶段链脲佐菌素诱导的糖尿病大鼠。STZ注射后两周,将BM-MNCs或载体盐水注射到单侧后肢肌肉中。SD大鼠的机械性痛觉过敏和冷异常性疼痛分别测量为von Frey毛发刺激和丙酮应用的足缩回次数。移植后2周检测大鼠坐骨神经运动传导速度(MNCV)、感觉神经传导速度(SNCV)、坐骨神经血流量(SNBF)、mRNA表达及组织学改变。BM-MNC移植显著改善了BM-MNC注射侧的机械性痛觉过敏和冷触诱发痛。此外,BM-MNC注射侧可改善糖尿病大鼠MNCV/SNCV减慢和SNBF降低。BM-MNC移植可改善大鼠后肢肌肉NT-3 mRNA表达和微血管数量的下降。骨髓单个核细胞移植对表皮内神经纤维密度无明显影响。这些结果表明,骨髓单个核细胞的自体移植可能是一种新的策略,用于治疗疼痛性糖尿病神经病变。
Relief from painful diabetic neuropathy is an important clinical issue. We have previously shown that the transplantation of cultured endothelial progenitor cells or mesenchymal stem cells ameliorated diabetic neuropathy in rats. In this study, we investigated whether transplantation of freshly isolated bone marrow-derived mononuclear cells (BM-MNCs) alleviates neuropathic pain in the early stage of streptozotocin-induced diabetic rats. Two weeks after STZ injection, BM-MNCs or vehicle saline were injected into the unilateral hind limb muscles. Mechanical hyperalgesia and cold allodynia in SD rats were measured as the number of foot withdrawals to von Frey hair stimulation and acetone application, respectively. Two weeks after the BM-MNC transplantation, sciatic motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), sciatic nerve blood flow (SNBF), mRNA expressions and histology were assessed. The BM-MNC transplantation significantly ameliorated mechanical hyperalgesia and cold allodynia in the BM-MNC-injected side. Furthermore, the slowed MNCV/SNCV and decreased SNBF in diabetic rats were improved in the BM-MNC-injected side. BM-MNC transplantation improved the decreased mRNA expression of NT-3 and number of microvessels in the hind limb muscles. There was no distinct effect of BM-MNC transplantation on the intraepidermal nerve fiber density. These results suggest that autologous transplantation of BM-MNCs could be a novel strategy for the treatment of painful diabetic neuropathy.
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