Combined Transplantation With Human Mesenchymal Stem Cells Improves Retinal Rescue Effect of Human Fetal RPE Cells in Retinal Degeneration Mouse Model

人类间充质干细胞联合移植可提高人胎儿 RPE 细胞在视网膜变性小鼠模型中的视网膜拯救效果

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作者:Ting Pan, Han Shen, Songtao Yuan, Guohua Lu, Yi Zhang, Hanxue Wang, Yazhi Zhao, Xincheng Sun, Qinghuai Liu

Conclusions

Combined transplantation of MSCs and fRPE cells results in a better retinal rescue effect than single cell type transplantation in NaIO3-induced retinopathy.

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.

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.

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.

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