Abstract：
Mesenchymal stromal cell (MSC) therapy for diabetic neuropathy (DN) has been extensively researched in vitro and in pre-clinical studies; however, the clinical scenario thus far has been disappointing. Temporary recovery, a common feature of these studies, indicates that either the retention of transplanted cells deteriorates with time or recovery of supportive endogenous cells, such as bone marrow-derived MSCs (BM-MSCs), does not occur, requiring further replenishment. In DN, BM-MSCs are recognized mediators of Schwann cell regeneration, and we have earlier shown that they suffer impairment in the pre-neuropathy stage. In this study, we attempted to further elucidate the mechanisms of functional recovery by focusing on changes occurring at the cellular level in the sciatic nerve, in conjunction with the biodistribution and movement patterns of the transplanted cells, to define the interval between doses.
We found that two doses of 1 × 106 dental pulp stromal cells (DPSCs) transplanted intramuscularly at an interval of 4 weeks effectively improved nerve conduction velocity (NCV) and restored motor coordination through improving sciatic nerve architecture, Schwann cell survival and myelination. Despite very minimal recovery of endogenous BM-MSCs, a temporary restoration of NCV and motor function was achieved with the first dose of DPSC transplantation. However, this did not persist, and a repeat dose was needed to consolidate functional improvement and rehabilitate the sciatic nerve architecture.
Thus, repeat intramuscular transplantation of DPSCs is more effective for maintenance of Schwann cell survival and myelination for functional recovery after onset of DN.
We found that two doses of 1 × 106 dental pulp stromal cells (DPSCs) transplanted intramuscularly at an interval of 4 weeks effectively improved nerve conduction velocity (NCV) and restored motor coordination through improving sciatic nerve architecture, Schwann cell survival and myelination. Despite very minimal recovery of endogenous BM-MSCs, a temporary restoration of NCV and motor function was achieved with the first dose of DPSC transplantation. However, this did not persist, and a repeat dose was needed to consolidate functional improvement and rehabilitate the sciatic nerve architecture.
Thus, repeat intramuscular transplantation of DPSCs is more effective for maintenance of Schwann cell survival and myelination for functional recovery after onset of DN.
摘要：
目的：间充质基质细胞（MSC）治疗糖尿病性神经病（DN）已在体外和临床前研究中得到了广泛的研究；然而，到目前为止，临床情况令人失望。临时恢复,这些研究的共同特点，表明移植细胞的保留随时间或支持性内源性细胞的恢复而恶化，如骨髓来源的MSCs（BM-MSCs），不会发生,需要进一步补充。在DN中，BM-MSCs是雪旺氏细胞再生的公认介质，我们早些时候已经表明，他们在神经病前阶段受到损害。在这项研究中,我们试图通过关注坐骨神经细胞水平的变化来进一步阐明功能恢复的机制，结合移植细胞的生物分布和运动模式，定义剂量之间的间隔。
结果：我们发现间隔4周的两次剂量的1×106个牙髓基质细胞（DPSC）肌内移植有效地改善了神经传导速度（NCV）并通过改善坐骨神经结构恢复了运动协调，雪旺氏细胞存活和髓鞘形成。尽管内源性BM-MSCs的回收非常小，首次给药DPSC移植可暂时恢复NCV和运动功能.然而,这并没有持续下去，并且需要重复剂量来巩固功能改善和恢复坐骨神经结构。
结论：因此，DPSC的重复肌内移植对于维持DN发病后的雪旺细胞存活和髓鞘形成功能恢复更有效。
结果：我们发现间隔4周的两次剂量的1×106个牙髓基质细胞（DPSC）肌内移植有效地改善了神经传导速度（NCV）并通过改善坐骨神经结构恢复了运动协调，雪旺氏细胞存活和髓鞘形成。尽管内源性BM-MSCs的回收非常小，首次给药DPSC移植可暂时恢复NCV和运动功能.然而,这并没有持续下去，并且需要重复剂量来巩固功能改善和恢复坐骨神经结构。
结论：因此，DPSC的重复肌内移植对于维持DN发病后的雪旺细胞存活和髓鞘形成功能恢复更有效。
