Effect of Mesenchymal Stem Cell-Derived Exosomes on Retinal Injury: A Review of Current Findings

Abstract

In recent years, various studies have followed in the literature on the therapeutic effects of mesenchymal stem cells (MSC) on damage in retinal cells. The evidence that MSCs exert their regenerative and damage reduction effect in a paracrine way, through the release of soluble factors and exosomes, is now consolidated. Exosomes are microvesicles formed by a double layer of phospholipid membrane and carry proteins and RNA, through which they play a therapeutic role on target cells. Scientific research has recently focused on the use of exosomes derived from MSC in various models of retinal damage in vitro and in vivo as they, compared to MSCs, have similar functions and at the same time have different advantages such as greater stability and handling, a lower chance of immunological rejection and no risk of malignant transformation. The purpose of this review is to summarize current knowledge on the therapeutic use of exosomes derived from MSCs in retinal damage and to stimulate new clinical perspectives regarding their use.

Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial–mesenchymal transition by targeting HOXC6

“…Thus, novel therapeutic methods need to be urgently developed to prevent vision loss and reduce subretinal scar formation in nAMD. The intravitreal administration of MSC has been reported to have an encouraging therapeutic effect on multiple retinal disease models, including retinal damage, inflammation, and nerve injury [23]. Despite the beneficial effects of MSCs in repairing retinal injury and restoring the visual system, their application is confined to ethical issues, poor diffusion through biological barriers, and possible complications such as epiretinal membranes, inflammatory response, and malignant transformation [31].…”

“…An increasing number of studies showed that exosomes secreted from MSCs could elicit significant therapeutic effects by suppressing fibrosis and improving their function in multiple-organ fibrosis models, such as liver, kidney, myocardium, and several retinal injury models [16][17][18][19][20][21][22][23]. In addition, studies also reported that the intravitreal injection of MSC-derived exosomes could ameliorate retinal laser injury by reducing damage and inhibiting apoptosis and inflammatory response [24].…”

Therapeutic Properties of Mesenchymal Stromal/Stem Cells: The Need of Cell Priming for Cell-Free Therapies in Regenerative Medicine

“…Currently, it is often stated that the efficacy of MSCs therapies is probably not related to cell engraftment and replacement but is linked to the production of crucial paracrine factors, such as cytokines, growth factors, and exosomes (EXOs), that regulate the cell niche for their regeneration. Indeed, in response to specific stimuli, MSCs are activated and can secrete a plethora of regulating factors that affect tissue injury responses in a transitory and paracrine manner to orchestrate the repairing tissue processes [ 20 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. In a different model of injury it has been shown that MSCs, mainly triggered by inflammation processes, induce tissue regeneration/repair by cell niche empowerment/regulation [ 45 , 46 , 47 ].…”

Effect of Stem Cell-Derived Extracellular Vesicles on Damaged Human Corneal Endothelial Cells

“…The treatment of pathologies and retinal damage with MSC-EVs typically takes place through intravitreal injection, allowing their direct action on the retinal cells and avoiding potential adverse effects towards other organs. Their use has been successfully studied in several diseases of the retina, such as retinal cell degeneration, refractory macular holes, and retinal detachments [ 35 – 77 ]. In all these cases, EVs have demonstrated a therapeutic effect, encouraging the realization of further studies.…”

“…A particularly promising area of investigation seems to be the use of extracellular vesicles derived by mesenchymal stem cells (MSC-EVs) that could be able to promote regeneration of damaged endothelium. MSC-EVs have been widely studied in various disease models [ 32 , 33 ], and in the last decade, they have been of interest in many ophthalmologic pathologies[ 34 , 35 ]. In 2018, indeed, it was evaluated the effect of MSC-EVs on corneal wound healing, and it was shown that human corneal MSC-EVs significantly increased the proliferation of human corneal epithelial cells in vitro and accelerated corneal wound closure in a murine epithelial mechanical injury model [ 36 ].…”