Liu Zhou, He Bing, Zhang Rong-Yi, Zhang Ke, Ding Ying, Ruan Jing-Wen, Ling Eng-Ang, Wu Jin-Lang, Zeng Yuan-Shan
Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Cell Transplant. 2015;24(7):1265-81. doi: 10.3727/096368914X682099. Epub 2014 May 22.
Transplantation of bone marrow mesenchymal stem cells (MSCs) promotes functional recovery in multiple sclerosis (MS) patients and in a murine model of MS. However, there is only a modicum of information on differentiation of grafted MSCs into oligodendrocyte-like cells in MS. The purpose of this study was to transplant neurotrophin-3 (NT-3) and retinoic acid (RA) preinduced MSCs (NR-MSCs) into a demyelinated spinal cord induced by ethidium bromide and to investigate whether EA treatment could promote NT-3 secretion in the demyelinated spinal cord. We also sought to determine whether increased NT-3 could further enhance NR-MSCs overexpressing the tyrosine receptor kinase C (TrkC) to differentiate into more oligodendrocyte-like cells, resulting in increased remyelination and nerve conduction in the spinal cord. Our results showed that NT-3 and RA increased transcription of TrkC mRNA in cultured MSCs. EA increased NT-3 levels and promoted differentiation of oligodendrocyte-like cells from grafted NR-MSCs in the demyelinated spinal cord. There was evidence of myelin formation by grafted NR-MSCs. In addition, NR-MSC transplantation combined with EA treatment (the NR-MSCs + EA group) reduced demyelination and promoted remyelination. Furthermore, the conduction of cortical motor-evoked potentials has improved compared to controls. Together, our data suggest that preinduced MSC transplantation combined with EA treatment not only increased MSC differentiation into oligodendrocyte-like cells forming myelin sheaths, but also promoted remyelination and functional improvement of nerve conduction in the demyelinated spinal cord.
骨髓间充质干细胞（MSCs）移植可促进多发性硬化症（MS）患者以及MS小鼠模型的功能恢复。然而，关于移植的MSCs在MS中分化为少突胶质细胞样细胞的信息却非常有限。本研究的目的是将神经营养因子-3（NT-3）和视黄酸（RA）预诱导的MSCs（NR-MSCs）移植到由溴乙锭诱导的脱髓鞘脊髓中，并研究电针治疗是否能促进脱髓鞘脊髓中NT-3的分泌。我们还试图确定增加的NT-3是否能进一步增强过表达酪氨酸受体激酶C（TrkC）的NR-MSCs分化为更多的少突胶质细胞样细胞，从而导致脊髓髓鞘再生增加和神经传导改善。我们的结果表明，NT-3和RA增加了培养的MSCs中TrkC mRNA的转录。电针增加了NT-3水平，并促进了脱髓鞘脊髓中移植的NR-MSCs向少突胶质细胞样细胞的分化。有证据表明移植的NR-MSCs形成了髓鞘。此外，NR-MSC移植联合电针治疗（NR-MSCs + EA组）减少了脱髓鞘并促进了髓鞘再生。此外，与对照组相比，皮质运动诱发电位的传导得到了改善。总之，我们的数据表明，预诱导的MSC移植联合电针治疗不仅增加了MSC向形成髓鞘的少突胶质细胞样细胞的分化，而且促进了脱髓鞘脊髓的髓鞘再生和神经传导功能的改善。
