Efficacy of implantation of hematopoietic mononuclear cells on diabetic peripheral neuropathy and foot ulcer.

1.本研究旨在观察外周血单个核细胞（PBMNCs）和骨髓单个核细胞（BMMNCs）移植对糖尿病周围神经病变血管生成的影响。6周龄雄性刘易斯大鼠静脉注射链脲佐菌素（50 mg/kg）。诱导糖尿病后4周，将6 × 10^7个PBMNC或1 × 10^8个BMMNC植入左后肢肌肉中。植入前后监测运动神经传导速度（MNCV）。在实验结束时，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4周后，PBMNCs组MNCV提高了54%， ...更多信息 BMMNC为67%（均p<0.01）。此外，植入的影响几乎被VEGF中和抗体的管理取消。糖尿病使坐骨神经NBF减少约50%（p<0.05）。通过植入PBMNCs和BMMNCs，灌注减少分别改善了74%和62%（分别为P<0.05和p<0.01）。这些影响仅在植入肢体中观察到。因子VIII的坐骨神经切片的免疫组织化学染色显示，在植入PBMNC或BMMNC后，坐骨神经中的血管数量没有显著增加。这些数据表明，造血单核细胞组分的植入与MNCV的改善有关，这是坐骨神经中的动脉生成效应的结果，VEGF可能有助于这种效应。这种改善发生在没有血管生成的情况下。因此，这些细胞片段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。少

1.Amelioration of diabetic peripheral neuropathy by implantation of hematopoietic mononuclear cells in Streptozotocin-induced diabetic rats.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 (50mg/kg) was injected intravenously into six-week-old male Lewis rats. Four weeks after the induction of diabetes, 6x10^7 of PBMNCs or 1x10^8 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 … More 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. Less