Amelioration of diabetic peripheral neuropathy by implantation of hematopoietic mononuclear cells in streptozotocin-induced diabetic rats
Amelioration of diabetic peripheral neuropathy by implantation of hematopoietic mononuclear cells in streptozotocin-induced diabetic rats
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DOI：
10.1016/j.expneurol.2005.11.001
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发表时间：
2006-06-01
影响因子：
5.3
通讯作者：
Iwasaka, Toshiji
中科院分区：
文献类型：
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作者：
Hasegawa, Takamasa;Kosaki, Atsushi;Iwasaka, Toshiji
进行本研究的目的是评估植入外周血单核细胞（PBMC）或骨髓单核细胞（BMMNC）对糖尿病周围神经病变的血管生成作用。将链脲佐菌素 (50 mg/kg) 静脉注射给 6 周大的雄性 Lewis 大鼠。诱导糖尿病4周后，将6×107个PBMNC或1×108个BMMNC植入左后肢肌肉中。在植入之前和之后监测运动神经传导速度（MNCV）。实验结束时，通过激光多普勒测量双侧神经血流量（NBF），并通过切片的因子VIII染色定量坐骨神经中的血管数量。糖尿病导致坐骨神经 MNCV 降低约 20% (P < 0.01)。植入后 4 周，PBMNC 的 MNCV 改善了 54%，BMMNC 的 MNCV 改善了 67%（均 P < 0.01）。此外，通过施用VEGF中和抗体，植入的效果几乎被消除。糖尿病使坐骨 NBF 减少约 50% (P < 0.05)。植入 PBMNC 可使灌注减少改善 74%，植入 BMMNC 可使灌注减少改善 62%（分别为 P < 0.05 和 P < 0.01）。这些效应仅在植入的肢体中观察到。坐骨神经切片的因子 VIII 免疫组织化学染色显示，植入 PBMNC 或 BMMNC 后，坐骨神经中的血管数量没有显着增加。这些数据表明，由于坐骨神经的动脉生成作用，造血单核细胞部分的植入与 MNCV 的改善相关，并且 VEGF 可能有助于这种作用。这种改善是在没有血管生成的情况下发生的。因此，这些细胞碎片的植入可能是治疗糖尿病周围神经病变的潜在新治疗方法。 (c) 2005 Elsevier Inc. 保留所有权利。
This study was performed in order to evaluate the angiogenic effect of implantation of either peripheral blood mononuclear cells (PBMNCs) or bone marrow mononuclear cells (BMMNCs) on diabetic peripheral neuropathy. Streptozotocin (50 mg/kg) was injected intravenously into 6-week-old mate Lewis rats. Four weeks after the induction of diabetes, 6 x 107 of PBMNCs or I x 108 of BMMNCs were implanted into the left hindlimb muscle. Motor nerve conduction velocity (MNCV) was monitored before and after implantation. At the end of the experiment, bilateral nerve blood flow (NBF) was measured by laser Doppler and the number of vessels in the sciatic nerves quantified by Factor VIII staining of the sections. Diabetes resulted in an approximately 20% reduction (P < 0.01) in sciatic MNCV. Four weeks after implantation, MNCV was improved by 54% with PBMNCs and by 67% with BMMNCs (both P < 0.01). Moreover, the effects of implantation were almost abolished by administration of VEGF-neutralizing antibody. Sciatic NBF was reduced by approximately 50% by diabetes (P < 0.05). This reduction in perfusion was improved by 74% by implantation of PBMNCs and by 62% by implantation of BMMNCs (P < 0.05 and P < 0.01, respectively). These effects were observed only in the implanted limb. Immunohistochemical staining of sciatic nerve sections for Factor VIII showed no significant increase in the number of vessels in the sciatic nerve following implantation of either PBMNCs or BMMNCs. These data suggest that implantation of hematopoietic mononuclear cell fractions is associated with an improvement in MNCV as a result of arteriogenic effects in the sciatic nerve, and that VEGF may contribute to this effect. This improvement occurred in the absence of angiogenesis. Implantation of these cell fractions may therefore be a potential new therapeutic method for treating diabetic peripheral neuropathy. (c) 2005 Elsevier Inc. All rights reserved.