Interleukin-13 Gene Modification Enhances Grafted Mesenchymal Stem Cells Survival After Subretinal Transplantation
- PDF / 3,690,794 Bytes
- 11 Pages / 595.276 x 790.866 pts Page_size
- 15 Downloads / 158 Views
ORIGINAL RESEARCH
Interleukin‑13 Gene Modification Enhances Grafted Mesenchymal Stem Cells Survival After Subretinal Transplantation Libin Huang1 · Junmei You1 · Yao Yao1 · Maosong Xie1 Received: 31 August 2019 / Accepted: 26 November 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019
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 Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10571-019-00768-3) contains supplementary material, which is available to authorized users. * Maosong Xie [email protected] Libin Huang [email protected] Junmei You [email protected] Yao Yao [email protected] 1
Department of Ophthalmology, The First Affiliated Hospital of Fujian Medical University, No. 20 Chazhong Road, 350005 Fuzhou, China
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 microsc
Data Loading...
