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

1.造血单个核细胞移植对糖尿病周围神经病变的改善本研究旨在探讨外周血单个核细胞(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。给6周龄雄性Lewis大鼠静脉注射链脲佐菌素(50 mg/kg)。糖尿病诱导4周后，将6×10~(-7)个PBMNC或1×10~(-8)个骨髓单个核细胞植入左侧后肢肌肉。分别于植入前后监测运动神经传导速度(MNCV)。实验结束后，激光多普勒测量双侧神经血流量，切片因子染色计数坐骨神经血管数。糖尿病导致坐骨神经MNCV减少约20%(p&lt；0.01)。植入4周后，PBMNC组和…组的MNCV改善了54%超过67%的人患有BMMNC(均为P&lt；0.01)。此外，给予血管内皮生长因子中和抗体后，植入效应几乎消失。糖尿病使坐骨神经NBF减少约50%(p&lt；0.05)。通过植入PBMNCs和植入BMMNCs，血流灌注的减少分别增加了74%和62%(分别为P&lt；0.05和P&lt；0.01)。这些影响仅在植入的肢体中观察到。免疫组织化学染色显示，植入PBMNCs或BMNCs后，坐骨神经中的血管数量没有明显增加。这些数据表明，由于坐骨神经的动脉生成效应，植入造血单核细胞组分与MNCV的改善有关，而血管内皮生长因子可能参与了这一效应。这种改善是在没有血管生成的情况下发生的。因此，植入这些细胞组分可能成为治疗糖尿病周围神经病变的一种潜在的新方法。较少

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