Dental pulp stem cells (DPSCs) have high proliferation and multi-differentiation capabilities that maintain their functionality after cryopreservation. In our previous study, we demonstrated that cryopreserved rat DPSCs improved diabetic polyneuropathy and that the efficacy of cryopreserved rat DPSCs was equivalent to that of freshly isolated rat DPSCs. The present study was conducted to evaluate whether transplantation of cryopreserved human DPSCs (hDPSCs) is also effective for the treatment of diabetic polyneuropathy. hDPSCs were isolated from human impacted third molars being extracted for orthodontic reasons. Eight weeks after the induction of diabetes in nude mice, hDPSCs (1 × 105/limb) were unilaterally transplanted into the hindlimb skeletal muscle, and vehicle (saline) was injected into the opposite side as a control. The effects of hDPSCs were analyzed at 4 weeks after transplantation. hDPSC transplantation significantly ameliorated reduced sensory perception thresholds, delayed nerve conduction velocity, and decreased the blood flow to the sciatic nerve in diabetic mice 4 weeks post-transplantation. Cultured hDPSCs secreted the vascular endothelial growth factor (VEGF) and nerve growth factor (NGF) proteins. A subset of the transplanted hDPSCs was localized around the muscle bundles and expressed the human VEGF and NGF genes at the transplanted site. The capillary/muscle bundle ratio was significantly increased on the hDPSC-transplanted side of the gastrocnemius muscles in diabetic mice. Neutralizing antibodies against VEGF and NGF negated the effects of hDPSC transplantation on the nerve conduction velocity in diabetic mice, suggesting that VEGF and NGF may play roles in the effects of hDPSC transplantation on diabetic polyneuropathy. These results suggest that stem cell transplantation with hDPSCs may be efficacious in treating diabetic polyneuropathy via the angiogenic and neurotrophic mechanisms of hDPSC-secreted factors.

中文翻译：

---

人牙髓干细胞的移植改善了链脲佐菌素诱导的糖尿病裸鼠的糖尿病多发性神经病：血管生成和神经营养因子的作用。

牙髓干细胞（DPSC）具有高增殖和多分化能力，可在冷冻保存后保持其功能。在我们以前的研究中，我们证明了冷冻保存的大鼠DPSC可以改善糖尿病性多发性神经病，并且冷冻保存的大鼠DPSC的功效与新鲜分离的大鼠DPSC相当。进行本研究以评估冷冻保存的人DPSC（hDPSC）的移植是否也有效治疗糖尿病多发性神经病。hDPSCs是从正畸原因中提取的受人类影响的第三磨牙中分离出来的。在裸鼠中诱发糖尿病八周后，将hDPSCs（1×105 /肢体）单侧移植到后肢骨骼肌中，并将媒介物（盐水）注射到对侧。移植后4周分析hDPSCs的作用。hDPSC移植显着改善了糖尿病小鼠在移植后4周时降低的感觉知觉阈值，延迟了神经传导速度并减少了到坐骨神经的血流量。培养的hDPSCs分泌了血管内皮生长因子（VEGF）和神经生长因子（NGF）蛋白。一部分移植的hDPSCs位于肌肉束周围，并在移植部位表达了人类VEGF和NGF基因。在糖尿病小鼠中，腓肠肌的hDPSC移植侧的毛细血管/肌束比率显着增加。抗VEGF和NGF的中和抗体可消除hDPSC移植对糖尿病小鼠神经传导速度的影响，提示VEGF和NGF可能在hDPSC移植对糖尿病多发性神经病的影响中发挥作用。这些结果表明，通过hDPSC分泌因子的血管生成和神经营养机制，用hDPSCs干细胞移植可能有效治疗糖尿病多发性神经病。