Combined Transplantation of Olfactory Ensheathing Cells With Rat Neural Stem Cells Enhanced the Therapeutic Effect in the Retina of RCS Rats
Combined Transplantation of Olfactory Ensheathing Cells With Rat Neural Stem Cells Enhanced the Therapeutic Effect in the Retina of RCS Rats
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DOI：
10.3389/fncel.2020.00052
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发表时间：
2020-03
影响因子：
5.3
通讯作者：
W. Zhai;Lixiong Gao;Ling-hui Qu;Yijian Li;Yuxiao Zeng;Qiyou Li;Haiwei Xu;Z. Yin
中科院分区：
文献类型：
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作者：
W. Zhai;Lixiong Gao;Ling-hui Qu;Yijian Li;Yuxiao Zeng;Qiyou Li;Haiwei Xu;Z. Yin
视网膜退行性疾病（RDDs）是致盲的主要原因，目前缺乏有效的治疗。细胞治疗已成为RDD的一种有前途的策略。嗅鞘细胞（OECs）或神经干细胞（NSCs）的移植最近已被应用于RDDs的实验性治疗。然而，单细胞移植的长期结果很差。多种细胞联合移植效果更佳。在本研究中，嗅鞘细胞[含嗅神经成纤维细胞（ONF）]和神经干细胞共移植到皇家外科学院（RCS）大鼠视网膜下腔。采用视网膜电图（ERG）、免疫荧光、Western blot和体外Transwell系统等方法，分别于术后4、8、12周观察单移植和联合移植的视网膜电生理和形态学变化，并探讨其可能机制。此外，利用Transwell系统，观察嗅鞘细胞对神经干细胞干性的影响。结果显示，与OECs或NSCs单独移植相比，OECs和NSCs联合移植在所有3个时间点均能显著改善ERG的b波振幅和外核层厚度。联合移植后，视网膜内发现更多的内源性干细胞。神经干细胞与嗅鞘细胞共移植后，胶质细胞酸性蛋白（GFAP）表达明显降低。联合移植组移植细胞的垂直和水平迁移均增强。同时，与嗅鞘细胞共培养后，神经干细胞的干细胞性也得到了较好的保持。结果表明，NSCs和OECs联合移植可增强RCS大鼠视网膜保护作用，为今后治疗视网膜发育障碍提供了新的策略。
Retinal degenerative diseases (RDDs) are the leading causes of blindness and currently lack effective treatment. Cytotherapy has become a promising strategy for RDDs. The transplantation of olfactory ensheathing cells (OECs) or neural stem cells (NSCs) has recently been applied for the experimental treatment of RDDs. However, the long-term outcomes of single-cell transplantation are poor. The combined transplantation of multiple types of cells might achieve better effects. In the present study, OECs [containing olfactory nerve fibroblasts (ONFs)] and NSCs were cotransplanted into the subretinal space of Royal College of Surgeons (RCS) rats. Using electroretinogram (ERG), immunofluorescence, Western blot, and in vitro Transwell system, the differences in the electrophysiological and morphological changes of single and combined transplantation as well as the underlying mechanisms were explored at 4, 8, and 12 weeks postoperation. In addition, using the Transwell system, the influence of OECs on the stemness of NSCs was discovered. Results showed that, compared to the single transplantation of OECs or NSCs, the combined transplantation of OECs and NSCs produced greater improvements in b-wave amplitudes in ERGs and the thickness of the outer nuclear layer at all three time points. More endogenous stem cells were found within the retina after combined transplantation. Glial fibrillary acidic protein (GFAP) expression decreased significantly when NSCs were cotransplanted with OECs. Both the vertical and horizontal migration of grafted cells were enhanced in the combined transplantation group. Meanwhile, the stemness of NSCs was also better maintained after coculture with OECs. Taken together, the results suggested that the combined transplantation of NSCs and OECs enhanced the improvement in retinal protection in RCS rats, providing a new strategy to treat RDDs in the future.