IMR Press / FBL / Volume 27 / Issue 3 / DOI: 10.31083/j.fbl2703086
Open Access Original Research
Mesenchymal stem cell derived exosomes-based immunological signature in a rat model of corneal allograft rejection therapy
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1 Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, 300384 Tianjin, China
*Correspondence: zhaosz1997@sina.com (Shaozhen Zhao)
These authors contributed equally.
Academic Editors: Shikun He and Graham Pawelec
Front. Biosci. (Landmark Ed) 2022, 27(3), 86; https://doi.org/10.31083/j.fbl2703086
Submitted: 9 December 2021 | Revised: 10 February 2022 | Accepted: 11 February 2022 | Published: 8 March 2022
(This article belongs to the Special Issue Recent Advances in Eye and Vision Research)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Mesenchymal stem cells (MSCs) are promising candidates for immunomodulatory therapy that are currently being tested in corneal allograft rejection. In this study, we tested the effects of Mesenchymal stem cells derived exosomes in the corneal allograft rejection model. Methods: Mesenchymal stem cells derived exosomes (MSC-exo) were collected and characterized. Wistar-Lewis rat corneal allograft rejection models were established. PKH26 labeled exosomes were used for track experiment. Models were randomly separated into four groups and treated with graded doses of exosomes or same volumn of PBS. Corneal grafts were assessed for rejection degree using slit-lamp biomicroscopy. Grafts were examined histologically using hematoxylin-eosin (H-E) staining and immunohistochemically using antibodies against CD4, CD8 and CD25. A comprehensive graft mRNA gene expression array analysis was conducted and checked by real-time polymerase chain reaction (PCR). Results: The nanovesicles obtained were expressing exosome specific protein markers CD9, CD63, CD81. The labeled exosomes could be detected in both cornea and anterior chamber two hours after injection.The 10 μg exosomes subconjunctival injection can effectively prolong graft survival time (MST 16.3 ± 2.5 days). 10 μg exosomes-treated group can inhibit the infiltration of CD4+ and CD25+ T cells. IFN-γ and CXCL11 levels were significantly decreased in grafts obtained from postoperative exosomes-treated rats when compared with controls. Conclusions: MSC-exo can cross biological barrier and play better role directly towards target tissue. MSC-exo can effectively prolong grafts survival time. Th1 signaling pathway was significantly inhibited in the exosomes treated group.

Keywords
mesenchymal stem cell
exosomes
cell-free immunomodulatory therapy
corneal allograft rejection
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