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Interleukin-13 Gene Modification Enhances Grafted Mesenchymal Stem Cells Survival After Subretinal Transplantation

  • Libin Huang
  • Junmei You
  • Yao Yao
  • Maosong XieEmail author
Original Research

Abstract

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.

Keywords

Mesenchymal stem cell Microglia Graft survival Interleukin-13 Subretinal transplantation Blood–retinal barrier 

Abbreviations

MSCs

Mesenchymal stem cells

MHC

Major histocompatibility complex

BRB

Blood–retinal barrier

RMG

Retinal microglia

IL-13

Interleukin-13

IL-13-MSCs

Interleukin-13 gene-modified mesenchymal stem cells

LV

Lentivirus

LPS

Lipopolysaccharides

RPE

Retinal pigment epithelium

TNF-α

Tumour necrosis factor-α

IL-1β

Interleukin-1β

IL-10

Interleukin-10

CNTF

Ciliary neurotrophic factor

GDNF

Glial cell-derived neurotrophic factor

ZO-1

Zonula occludens-1

SEM

Scanning electron microscopy

Notes

Author Contributions

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.

Funding

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.

Ethical Approval

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.

Supplementary material

10571_2019_768_MOESM1_ESM.docx (599 kb)
Supplementary material 1 (DOCX 599 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of OphthalmologyThe First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

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