Combined Transplantation With Human Mesenchymal Stem Cells Improves Retinal Rescue Effect of Human Fetal RPE Cells in Retinal Degeneration Mouse Model
Combined Transplantation With Human Mesenchymal Stem Cells Improves Retinal Rescue Effect of Human Fetal RPE Cells in Retinal Degeneration Mouse Model
复制标题
与人间充质干细胞联合移植提高人胎儿RPE细胞在视网膜变性小鼠模型中的视网膜拯救效果
DOI：
10.1167/iovs.61.8.9
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发表时间：
2020
影响因子：
4.4
通讯作者：
Liu Qinghuai
中科院分区：
文献类型：
--
作者：
Pan Ting;Shen Han;Yuan Songtao;Lu Guohua;Zhang Yi;Wang Hanxue;Zhao Yazhi;Sun Xincheng;Liu Qinghuai
目的在视网膜变性疾病小鼠模型中验证胎儿视网膜色素上皮细胞（fRPE）和间充质干细胞（MSCs）联合移植是否能联合收割机结合这两种细胞的特性并减轻视网膜变性。方法尾静脉注射碘酸钠（NaIO 3）建立视网膜变性疾病小鼠模型。将MSC和fRPE细胞单独或组合移植到视网膜变性疾病动物的视网膜下腔中。进行ERG、光学相干断层扫描、组织学和免疫荧光分析。此外，Crx，视紫红质，Iba 1，F4/80，Caspase 3，神经生长因子和脑源性神经营养因子的表达水平进行了评估，以探讨细胞移植效应的机制。结果fRPE和MSC细胞联合移植可明显改善视网膜电图结果，并提高移植细胞的存活率。此外，MSC和fRPE细胞共移植导致总视网膜厚度以及外核层和内核层厚度增加。联合移植还上调了Crx和视紫红质的表达水平，下调了caspase 3的表达，突出了与单细胞型移植相关的更好的光感受器拯救效果。最后，联合移植抑制了Iba 1和F4/80因子的表达，同时增加了内源性神经生长因子和脑源性神经生长因子神经营养因子的表达。这些数据表明MSC和fRPE细胞共移植能够抑制免疫反应并促进神经营养因子的分泌。结论MSCs和fRPE细胞联合移植对NaIO 3诱导的视网膜病变的挽救效果优于单细胞移植。
Purpose We verified whether fetal RPE (fRPE) cells and mesenchymal stem cells (MSCs) cotransplantation can combine the features of these two cell types and alleviate retinal degeneration in a retinal degenerative disease mouse model. Methods Tail vein injection of sodium iodate (NaIO3) was conducted to establish the retinal degenerative disease mouse model. MSCs and fRPE cells were transplanted either separately or combined in the subretinal space of retinal degenerative disease animals. ERG, optical coherence tomography, histologic, and immunofluorescence analyses were performed. Furthermore, the expression level of Crx, rhodopsin, Iba1, F4/80, Caspase 3, nerve growth factor, and brain-derived neurotrophic factor were assessed to investigate the mechanisms involved in cell transplantation effects. Results Cotransplantation of fRPE and MSC cells promoted significant improvements in ERG results and in the survival rate of transplanted cells. In addition, MSC and fRPE cell cotransplantation resulted in an increase in the thickness of the total retina, as well as in the outer and inner nuclear layers. Combined transplantation also upregulated the expression level of Crx and rhodopsin and downregulated caspase 3 expression, highlighting its better photoreceptor rescue effect in relation to the single cell type transplantation. Finally, combined transplantation suppressed the expression of Iba1 and F4/80 factors while increasing the endogenous expression of nerve growth factor and brain-derived nerve growth factor neurotrophic factors. These data suggest that MSC and fRPE cell cotransplantation is able to suppress immunoreactions and promote neurotrophic factor excretion. Conclusions Combined transplantation of MSCs and fRPE cells results in a better retinal rescue effect than single cell type transplantation in NaIO3-induced retinopathy.