Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Nov 26, 2019; 11(11): 957-967
Published online Nov 26, 2019. doi: 10.4252/wjsc.v11.i11.957
Cytokine interplay among the diseased retina, inflammatory cells and mesenchymal stem cells - a clue to stem cell-based therapy
Vladimir Holan, Barbora Hermankova, Magdalena Krulova, Alena Zajicova
Vladimir Holan, Barbora Hermankova, Magdalena Krulova, Alena Zajicova, Department of Transplantation Immunology, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague 14220, Czech Republic
Vladimir Holan, Barbora Hermankova, Magdalena Krulova, Department of Cell Biology, Faculty of Science, Charles University, Prague 12843, Czech Republic
Author contributions: All authors reviewed the literature, contributed to writing, and approved the manuscript.
Supported by the Grant Agency of the Czech Republic, No. 17-04800S, No. 18-04393S, No. 19-02290S; the Ministry of Education, Youth and Sports of the Czech Republic, No. SVV 244-260435, No. NPU-I: LO1508, No. NPU-I: LO1309.
Conflict-of-interest statement: The authors declare no conflicts of interest.
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 Non Commercial (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:
Corresponding author: Vladimir Holan, PhD, Professor, Department of Transplantation Immunology, Institute of Experimental Medicine of the Czech Academy of Sciences, Videnska 1083, Prague 14220, Czech Republic.
Telephone: +420-241063226
Received: May 25, 2019
Peer-review started: May 27, 2019
First decision: July 31, 2019
Revised: September 2, 2019
Accepted: September 13, 2019
Article in press: September 13, 2019
Published online: November 26, 2019

Retinal degenerative disorders, such as diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration or glaucoma, represent the most common causes of loss of vision and blindness. In spite of intensive research, treatment options to prevent, stop or cure these diseases are limited. Newer therapeutic approaches are offered by stem cell-based therapy. To date, various types of stem cells have been evaluated in a range of models. Among them, mesenchymal stem/stromal cells (MSCs) derived from bone marrow or adipose tissue and used as autologous cells have been proposed to have the potential to attenuate the negative manifestations of retinal diseases. MSCs delivered to the vicinity of the diseased retina can exert local anti-inflammatory and repair-promoting/regenerative effects on retinal cells. However, MSCs also produce numerous factors that could have negative impacts on retinal regeneration. The secretory activity of MSCs is strongly influenced by the cytokine environment. Therefore, the interactions among the molecules produced by the diseased retina, cytokines secreted by inflammatory cells and factors produced by MSCs will decide the development and propagation of retinal diseases. Here we discuss the interactions among cytokines and other factors in the environment of the diseased retina treated by MSCs, and we present results supporting immunoregulatory and trophic roles of molecules secreted in the vicinity of the retina during MSC-based therapy.

Keywords: Retina, Degenerative diseases, Stem cell therapy, Mesenchymal stem cells, Cytokines, Growth factors

Core tip: Cell-based therapy using autologous mesenchymal stem cells represents a perspective approach for the treatment of so far incurable degenerative retinal diseases. However, the therapeutic potential of mesenchymal stem cells strongly depends on the cytokine environment, where these cells are delivered. In this study, we discuss recent knowledge regarding the interactions and interplay among cytokines produced by cells of the diseased retina, inflammatory immune cells and therapeutically administered mesenchymal stem cells. We suggest that these interactions among cytokines and growth factors occurring in the microenvironment of the diseased retina could be critical for the outcome of the stem cell-based therapy for retinal disorders.