Adult Stem Cells, Tools for Repairing the Retina

Abstract

Purpose: Retinal degenerative diseases lead to the death of retinal neurons causing visual impairment and blindness. In lower order vertebrates, the retina and its surrounding tissue contain stem cell niches capable of regenerating damaged tissue. Here we examine these niches and review their capacity to be used as retinal stem/progenitor cells (RSC/RPCs) for retinal repair. Recent Findings: Exogenous factors can control the in vitro activation of RSCs/PCs found in several niches within the adult eye including cells in the ciliary margin, the retinal pigment epithelium, iris pigment epithelium as well as the inducement of Müller and amacrine cells within the neural retina itself. Recently, factors have been identified for the activation of adult mammalian Müller cells to a RPC state in vivo. Summary: Whereas cell transplantation still holds potential for retinal repair, activation of the dormant native regeneration process may lead to a more successful process including greater integration efficiency and proper synaptic targeting.

Management of retinitis pigmentosa by Wharton’s jelly derived mesenchymal stem cells: preliminary clinical results

“…MSCs produce exosomes that contain growth factors, mRNA, microRNA and mitochondrial companents. This content ensures that the exosomes are long-acting [42][43][44].. MSCs are nonhematopoietic multipotent stromal cells that can be isolated from different sources, including bone marrow, adipose tissue, umbilical cord tissue, cord blood, placenta, dental pulp and amniotic fluid [12,45,46]. Umbilical cord Wharton's jelly derived mesenchymal stem cells (WJ-MSCs) are superior to other cell types in retinal degeneration in terms of how easily we can obtain these cells, as well as their tissue compatibility, rapid proliferation, long-term efficacy in the transplanted tissue, high paracrine effect, immunomodulation effect, non-tumoral side effect, and because these cells have similar features as the retinal pigment epithelium [13][14][15][16][17][18][19][20][21].…”

“…Molecules greater than 75 kDa can be dispersed through the sclera by changing the electrical charges using electrical/electromagnetic iontophoresis such as Magnovision™ [59][60][61][62][63][64]. Growth factors secreted by MSCs in the subretinal space activate the cells in the dormant phase and stimulate the progenitor cells (embriyonic remnants) in the retina [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]29]. We preferred to use the deep sub-tenon space as a microenvironment in order to prevent the devastating adverse effects of intravitreal/subretinal injection.…”

“…WJ-MSCs also undergo less nuclear and mitochondrial mutations compared to MSCs collected from adult tissues. WJ-MSCs do not stimulate T-cell proliferation because they do not express MHC class II [45,46].. WJ-MSCs have an effect on activated macrophages, reducing the secretion of inflammatory factors [12][13][14][15][16][17][18][19][20][21]. MSCs secrete factors that support cell survival and regulate adjacent cells in damaged tissue; hence, they can rescue the damaged naive nature of MSCs derived from an umbilical cord.…”

“…Growth factors obtained from PRP last for 4-6 months and require booster injections. Adipose MSCs can proliferate in tissues 5 times without karyotype changes [12,45,46] and WJ-MSCs can proliferate 25-300 times without karyotype changes [12-21, 45, 56]. This means that the paracrine-trophic effects of WJ-MSCs may persist for 3-7 years in the tissue where they are transplanted allogeneically.…”

“…Umbilical cord Wharton's jelly derived mesenchymal stem cells (WJ-MSCs) have significant paracrine and immunomodulatory properties [12][13][14][15][16][17][18]. WJ-MSCs secrete trophic factors that stimulate RPE or secrete trophic factors that are similar to those produced by RPE [19][20][21].…”