Evaluation of the Potential Effects of Retinol and Alginate/Gelatin-Based Scaffolds on Differentiation Capacity of Mouse Mesenchymal Stem Cells (MSCs) into Retinal Cells

Abstract

Background and Objectives Retinal stem cells (RSCs) resided in ciliary epithelium have shown to possess a high capacity to self-renew and differentiate into retinal cells. RSCs could be induced to differentiate when they are exposed to stimuli like natural compounds and suitable contexts such as biomaterials. The aim of this study was to examine the effects of Retinol and alginate/gelatin-based scaffolds on differentiation potential of mesenchymal stem cells (MSCs) originated from mouse ciliary epithelium. Methods and Results MSCs were extracted from mouse ciliary epithelium, and their identity was verified by detecting specific surface antigens. To provide a three-dimensional in vitro culture system, 2% alginate, 0.5% gelatin and the mixed alginate-gelatin hydrogels were fabricated and checked by SEM. Retinol treatment was performed on MSCs expanded on alginate/gelatin hydrogels and the survival rate and the ability of MSCs to differentiate were examined through measuring expression alterations of retina-specific genes by ICC and qPCR. The cell population isolated from ciliary epithelium contained more than 93.4% cells positive for MSC-specific marker CD105. Alginate/gelatin scaffolds showed to provide an acceptable viability (over 70%) for MSC cultures. Retinol treatment could induce a high expression of rhodopsin protein in MSCs expanded in alginate and alginate-gelatin mixtures. An elevated presentation of Nestin , RPE65 and Rhodopsin genes was detected in retinol-treated cultures expanded on alginate and alginate-gelatin scaffolds. Conclusions The results presented here elucidate that retinol treatment of MSCs grown on alginate scaffolds would promote the mouse ciliary epithelium-derived MSCs to differentiate towards retinal neurons.

Retinol-Loaded Poly(vinyl alcohol)-Based Hydrogels as Suitable Biomaterials with Antimicrobial Properties for the Proliferation of Mesenchymal Stem Cells

“…The BMMS cells’ proliferative effect of PVA hydrogel was significantly improved by the incorporation of retinol from 0.1 to 0.5 wt.%. Several studies already claimed the beneficial effect of retinol in stem cell proliferation, metabolism, and differentiation [ 86 , 87 , 88 , 89 , 90 , 91 ]. The differentiation potential of mesenchymal stem cells originated from mouse ciliary epithelium into retinal neurons by retinol treatment and could be achieved through elevating the expression of the rhodopsin protein and the Nestin, RPE65, and Rhodopsin genes [ 90 ].…”

“…Several studies already claimed the beneficial effect of retinol in stem cell proliferation, metabolism, and differentiation [ 86 , 87 , 88 , 89 , 90 , 91 ]. The differentiation potential of mesenchymal stem cells originated from mouse ciliary epithelium into retinal neurons by retinol treatment and could be achieved through elevating the expression of the rhodopsin protein and the Nestin, RPE65, and Rhodopsin genes [ 90 ]. It was also stated that retinol affects the differentiation potential of gingival progenitor stem cells through activating Wnt/β-catenin signals, and the differentiation of MSCs into neural cells could be achieved by retinol treatment through upregulating the expression of vimentin, Stra13, and RARα/β/γ and downregulating Brachyury expression [ 91 ].…”