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

Table 2 Summary of the main results obtained in mesenchymal stem cell-based experiments for glaucoma

MSC source	Treatment	Results	Ref.
Rat BMSCs	In vitro co-cultures of BMSCs with pigmented cells from ciliary margin	Enhanced expression of cone-rod homeobox, at both mRNA and protein level	Li et al[43], 2017
Mouse BMSCs	BMSC injection into the ocular anterior chamber of a laser-induced rat model	Decreased intraocular pressure likely due to MSC paracrine activity	Manuguerra-Gagné et al[44], 2013
Rat BMSCs	BMSC injection into the ocular anterior chamber of a rat model obtained by cauterization of episcleral veins	Reduced intraocular pressure, associated to MSC engrafting to the ciliary processes and to the trabecular meshwork	Roubeix et al[45], 2015
	BMSC-conditioned medium treatment of TGF-β2-induced fibrotic human trabecular meshwork cell cultures	Improved survival of trabecular meshwork cells, by activation of anti-apoptotic signaling pathway Akt
Rat BMSCs	Intravitreal or intravenous administration of labeled BMSCs in a laser-induced ocular hypertension rat model	Local but not systemic BMSC administration improved retinal ganglion cell survival. Transplanted BMSCs were preferentially located in a perivascular position	Johnson et al[47], 2010
Rat/humanBMSCs	Co-cultures of retinal explants with rat and human BMSCs, or rat and human fibroblasts	BMSCs but not fibroblasts improved retinal ganglion cell survival. An increased density of cells expressing islet-1 and NeuN was found in retinal ganglion cell layer	Johnson et al[48], 2014
	Exposure of retinal explant cultures to conditioned media from BMSCs or fibroblast	Moderate improvements were observed only for BMSC conditioned medium treatment
Human BMSCs	Intravitreal injections of extracellular vesicles obtained from BMSCs of fibroblasts in two rat models of glaucoma	BMSC extracellular vesicles more efficiently reduced retinal ganglion cell apoptosis	Mead et al[38], 2018
Engineered mouse BMSCs	Indirect co-cultures of BMSCs with retinal ganglion cells in a transwell system	BMSCs enhanced anti-apoptotic effects on retinal ganglion cells by upregulation of stanniocalcin-1. Improved effects were obtained by miRNA-21-overexpressing BMSCs	Su et al[49], 2017
Autologous BMSCs	Clinical trial carried out by intravitreal injection of autologous BMSCs in patients with advanced stage of glaucoma	No significant improvements were reported	Vilela et al[50], 2021

MSCs: Mesenchymal stem cells; TGF: Transforming growth factor; BMSCs: Bone marrow stem cells; miRNA: MicroRNA.