Retina stem cells, hopes and obstacles

GERMAN, OLGA L; VALLESE-MAURIZI, HARMONIE; SOTO, TAMARA B; ROTSTEIN, NORA P; POLITI, LUIS ENRIQUE

World Journal of Stem Cells

Baishideng Publishing Group Inc

Año: 2021 vol. 13 p. 1446 - 1479

1948-0210

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-vascularendothelial growth factor and many survival and trophic factors that, in somecases, slow down the progression of the degeneration, but do not effectivelyprevent it. The finding of stem cells (SC) in the eye has led to the proposal of cellreplacement strategies for retina degeneration. Therapies using different types ofSC, such as retinal progenitor cells (RPCs), embryonic SC, pluripotent SCs (PSCs),induced PSCs (iPSCs), and mesenchymal stromal cells, capable of self-renewaland of differentiating into multiple cell types, have gained ample support.Numerous preclinical studies have assessed transplantation of SC in animalmodels, with encouraging results. The aim of this work is to revise the differentpreclinical and clinical approaches, analyzing the SC type used, their efficacy,safety, cell attachment and integration, absence of tumor formation andimmunorejection, in order to establish which were the most relevant andsuccessful. In addition, we examine the questions and concerns still open in thefield. The data demonstrate the existence of two main approaches, aimed atreplacing either RPE cells or photoreceptors. Emerging evidence suggests thatRPCs and iPSC are the best candidates, presenting no ethical concerns and a lowrisk of immunorejection. Clinical trials have already supported the safety andefficacy of SC treatments. Serious concerns are pending, such as the risk of tumorformation, 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 effectivetreatments to restore vision loss in a near future.