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World J Stem Cells. Oct 26, 2021; 13(10): 1446-1479
Published online Oct 26, 2021. doi: 10.4252/wjsc.v13.i10.1446
Retina stem cells, hopes and obstacles
Olga L German, Harmonie Vallese-Maurizi, Tamara B Soto, Nora P Rotstein, Luis Enrique Politi
Olga L German, Harmonie Vallese-Maurizi, Nora P Rotstein, Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, Bahia blanca 8000, Buenos Aires, Argentina
Olga L German, Harmonie Vallese-Maurizi, Tamara B Soto, Nora P Rotstein, Luis Enrique Politi, Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, and Neurobiology Department, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) Conicet, Bahía Blanca 8000, Buenos Aires, Argentina
Author contributions: Politi LE, Rotstein NP and German OL wrote the paper; Politi LE, Rotstein NP, German OL, Soto TB and Vallese-Maurizi H corrected the text; Soto TB and Vallese-Maurizi H prepared glial cultures; Soto TB took the pictures, and figures; Politi LE designed and made the Figures.
Supported by National Research Council of Argentina (CONICET), No. PIP 11220-1101-00827; National Agency for Science and Technology (ANPCYT), No. PICT-2016-0353 and No. PICT-2016-0475; Secretary of Science and Technology, Universidad Nacional del Sur (UNS), No. 24-B190 and No. 24/ZB68.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Luis Enrique Politi, PhD, Associate Full Professor (RE), Doctor, Research Scientist, Department of Biology, Biochemistry and Pharmacy, Universidad Nacional del Sur, and Neurobiology Department, Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB) Conicet, Camino la Carrindanga 7000, Bahía Blanca 8000, Buenos Aires, Argentina. inpoliti@criba.edu.ar
Received: April 28, 2021
Peer-review started: April 28, 2021
First decision: June 23, 2021
Revised: July 14, 2021
Accepted: September 14, 2021
Article in press: September 14, 2021
Published online: October 26, 2021
Processing time: 180 Days and 13 Hours
Abstract

Retinal degeneration is a major contributor to visual dysfunction worldwide. Although it comprises several eye diseases, loss of retinal pigment epithelial (RPE) and photoreceptor cells are the major contributors to their pathogenesis. Early therapies included diverse treatments, such as provision of anti-vascular endothelial growth factor and many survival and trophic factors that, in some cases, slow down the progression of the degeneration, but do not effectively prevent it. The finding of stem cells (SC) in the eye has led to the proposal of cell replacement strategies for retina degeneration. Therapies using different types of SC, such as retinal progenitor cells (RPCs), embryonic SC, pluripotent SCs (PSCs), induced PSCs (iPSCs), and mesenchymal stromal cells, capable of self-renewal and of differentiating into multiple cell types, have gained ample support. Numerous preclinical studies have assessed transplantation of SC in animal models, with encouraging results. The aim of this work is to revise the different preclinical and clinical approaches, analyzing the SC type used, their efficacy, safety, cell attachment and integration, absence of tumor formation and immunorejection, in order to establish which were the most relevant and successful. In addition, we examine the questions and concerns still open in the field. The data demonstrate the existence of two main approaches, aimed at replacing either RPE cells or photoreceptors. Emerging evidence suggests that RPCs and iPSC are the best candidates, presenting no ethical concerns and a low risk of immunorejection. Clinical trials have already supported the safety and efficacy of SC treatments. Serious concerns are pending, such as the risk of tumor formation, lack of attachment or integration of transplanted cells into host retinas, immunorejection, cell death, and also ethical. However, the amazing progress in the field in the last few years makes it possible to envisage safe and effective treatments to restore vision loss in a near future.

Keywords: Retina regeneration; Stem cells; Retina stem cell transplantation; Cancer stem cells; Photoreceptor replacement

Core Tip: Retinal degeneration is a major cause of visual loss worldwide, having no cure or suitable treatments. Transplantation of stem cells into the eye to replace lost cells is being evaluated as a new therapeutic strategy. Establishing the most suitable source of stem cells and ethical and safety concerns still require to be solved. Preclinical studies and ongoing clinical trials support stem cells as a promising therapeutic approach to restore vision loss.