Interleukin-13 Gene Modification Enhances Grafted Mesenchymal Stem Cells Survival After Subretinal Transplantation.
Blood–retinal barrier
Graft survival
Interleukin-13
Mesenchymal stem cell
Microglia
Subretinal transplantation
Journal
Cellular and molecular neurobiology
ISSN: 1573-6830
Titre abrégé: Cell Mol Neurobiol
Pays: United States
ID NLM: 8200709
Informations de publication
Date de publication:
Jul 2020
Jul 2020
Historique:
received:
31
08
2019
accepted:
26
11
2019
pubmed:
4
12
2019
medline:
26
1
2021
entrez:
4
12
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31792777
doi: 10.1007/s10571-019-00768-3
pii: 10.1007/s10571-019-00768-3
doi:
Substances chimiques
Interleukin-13
0
Nerve Growth Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
725-735Subventions
Organisme : Startup Fund for scientific research of Fujian Medical University
ID : 2016QH041
Organisme : Fund for Young and Middle-aged University Teachers' educational research of Fujian Province
ID : JT180188
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