Potential therapeutic applications of mesenchymal stem cells for the treatment of eye diseases

Table 3 Summary of the main results obtained in mesenchymal stem cell-based experiments for retinitis pigmentosa

MSC source	Treatment	Results	Ref.
ConjunctivaMSCs	Retinal-like MSC differentiation in 3D scaffold fibrin gel, by an induction medium containing taurine	Increased expression of typical retinal markers (nestin, rhodopsin, and RPE65)	Soleimannejad et al[68], 2017
Rat BMSCs	Intravitreal BMSC injections in a rat model of retina degeneration	Increased expression of typical photoreceptor marker (rhodopsin) and retinal pigment epithelium (pancytokeratin)	Huo et al[65], 2010
Mouse BMSCs	BMSC injections in the subretinal space of rhodopsin knockout mice	MSC engrafting in retinal pigment epithelium and neuroretina, acquiring neuronal and glial morphology, and prolonging photoreceptor survival	Arnhold et al[69], 2007
Rat BMSCs	Intravenous BMSC administration in a rat model of retinitis pigmentosa, before photoreceptor loss	Rod and cone cell preservation. Improved visual functions	Wang et al[70], 2010
Mouse ASCs/human UCMSCs	Intravitreal MSC or their exosomes in a laser-induced mouse model of retinal injury	Both MSCs and their exosomes reduced retinal damage, apoptosis and inflammatory responses	Yu et al[71], 2016
Human BMSCs	Physically separated co-cultures of BMSCs with porcine neuroretina	BMSC secretomes induced increased levels of anti-inflammatory cytokines, antioxidant and anti-apoptotic proteins, and anti-neurodegeneration proteins, Photoreceptors and the retinal general organization were better preserved	Usategui-Martìn et al[72], 2020
Engineered human UCMSCs	Photoreceptor-like differentiation of UCMSCs overexpressing erythropoietin, by an induction medium containing taurine	Transduced UCMSCs better overexpressed cone-rod homeobox and rhodopsin	Ding et al[73], 2019
Engineered human BMSCs	Photoreceptor-like differentiation of BMSCs overexpressing miRNA-183/96/182 cluster	Transduced BMSCs overexpressed recoverin, a neuronal calcium-binding protein primarily detected in photoreceptors.	Mahmoudian-Sani et al[74], 2019
Engineered conjunctiva MSCs	Photoreceptor-like differentiation of MSCs overexpressing miRNA-9	In a time dependent manner, MSCs overexpressed photoreceptor markers recoverin, rhodopsin, PKC, and peripherin	Rahmani et al[75], 2020
Engineered mouse BMSCs	Intravitreal injections of BMSCs genetically modified to overexpress neurotrophin-4, in a mouse model of retinopathy	Neurotrophin-4-overexpressing BMSCs induced a significant retinal protection, as indicated by bioelectrical recordings and optical coherence tomography.	Machalińska et al[76], 2013
Autologous MSCs	In a phase I clinical trial, the safety, feasibility, and efficacy of autologous BMSC was tested after their intravitreal injection in patients with advanced retinitis pigmentosa	In spite of several mild and transient adverse effects, a significant improvement of best corrected visual acuity was observed. Only one severe, though manageable adverse effect was observed after three years	Tuekprakhon et al[77], 2021
Human UCMSCs	In a phase 3 clinical study, UCMSC administration was carried out by surgical procedures in the suprachoroidal area of 82 patients with retinitis pigmentosa	Over 6-month follow-up period, no serious adverse events were reported. Significant improvements were detected for best corrected visual acuity, visual field and multifocal electroretinography recordings. Beneficial effects might be due to MSC secretion of growth factors.	Kahraman et al[78], 2020
Human UCMSCs	In a phase I/II clinical trial, the protocol safety and efficacy was tested by intravenous administration of UCMSCs in 32 patients with advanced retinitis pigmentosa	The intravenous infusion of UCMSCs was safe, since no serious local or systemic adverse effects occurred over a period of 12 mo. Most patients improved their best corrected visual acuity, especially in the first 3 months. It was concluded that this strategy may improve the quality of life of patients with retinitis pigmentosa.	Zhao et al[79], 2020

ASCs: Adipose tissue stem cells; MSCs: Mesenchymal stem cells; TGF: Transforming growth factor; BMSCs: Bone marrow stem cells; UCMSCs: Umbilical cord mesenchymal stem cells.