Interleukin-13 Gene Modification Enhances Grafted Mesenchymal Stem Cells Survival After Subretinal Transplantation
Mesenchymal stem cells (MSCs) hold great potential for cell- and gene-based therapies for retinal degeneration. Limited survival is the main obstacle in achieving successful subretinal transplantation of MSCs. The present study sought to evaluate the effect of interleukin-13 (IL-13) gene modification on the phenotypic alteration of retinal microglia (RMG) and the survival of MSCs following subretinal grafting. In this study, LPS-activated RMG were cocultured with MSCs or IL-13-expressing MSCs (IL-13-MSCs) for 24 h, and activated phenotypes were detected in vitro. Western blotting was performed to quantify cytokine secretion by light-injured retinas following subretinal transplantation. The numbers of activated RMG and surviving grafted cells were analysed, and the integrity of the blood–retinal barrier (BRB) was examined in vivo. We found that, compared with normal MSCs, cocultured IL-13-MSCs suppressed the expression of pro-inflammatory factors and major histocompatibility complex II, promoted the expression of anti-inflammatory cytokines by activated RMG and simultaneously inhibited the proliferation of and phagocytosis by RMG. The subretinal transplantation of IL-13-MSCs increased the expression of neurotrophic factors, IL-13 and tight junction proteins in the host retina, decreased the number of phagocytic RMG and improved the survival of grafted cells. Furthermore, IL-13-MSCs alleviated BRB breakdown induced by subretinal injection. Our results demonstrate that IL-13-MSCs can polarize activated RMG to the neuroprotective M2 phenotype and enhance the survival of grafted MSCs against the damage stress induced by subretinal transplantation.
KeywordsMesenchymal stem cell Microglia Graft survival Interleukin-13 Subretinal transplantation Blood–retinal barrier
Mesenchymal stem cells
Major histocompatibility complex
Interleukin-13 gene-modified mesenchymal stem cells
Retinal pigment epithelium
Tumour necrosis factor-α
Ciliary neurotrophic factor
Glial cell-derived neurotrophic factor
Scanning electron microscopy
HL performed and analysed majority of all experiments, including cell coculture and subretinal transplantation. XM and YJ participated in most of the experiments. HL and YY conceived and designed the experiments. The manuscript was written by HL, XM and YJ. All authors read and approved the final manuscript.
This study was supported by grants from Startup Fund for scientific research of Fujian Medical University (Grant Number: 2016QH041), and Fund for Young and Middle-aged University Teachers’ educational research of Fujian Province (Grant Number: JT180188).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no competing interests.
All animal procedures were approved by the Animal Care and Use Committee of the First Affiliated Hospital of Fujian Medical University (no.2016-YK-163) and conformed to the Association for Research in Vision and Ophthalmology (ARVO) Statement on the Use of Animals in Ophthalmic and Vision Research. All efforts were resorted to minimize the number of rats used and their suffering.
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