The Identification of Interferon-γ as a Key Supportive Factor for Retinal Differentiation of Murine Mesenchymal Stem Cells
Language English Country United States Media print-electronic
Document type Journal Article
PubMed
28728472
DOI
10.1089/scd.2017.0111
Knihovny.cz E-resources
- Keywords
- differentiation, interferon-γ, mesenchymal stem cell, neurotrophic factor, retina, rhodopsin,
- MeSH
- Cell Differentiation * MeSH
- cis-trans-Isomerases genetics metabolism MeSH
- Interferon-gamma pharmacology MeSH
- Calbindin 2 genetics metabolism MeSH
- Cells, Cultured MeSH
- Mesenchymal Stem Cells cytology drug effects metabolism MeSH
- Mice, Inbred BALB C MeSH
- Mice MeSH
- Recoverin genetics metabolism MeSH
- Retina cytology metabolism MeSH
- Rhodopsin genetics metabolism MeSH
- Carrier Proteins genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 11-cis-retinal-binding protein MeSH Browser
- cis-trans-Isomerases MeSH
- Interferon-gamma MeSH
- Calbindin 2 MeSH
- Recoverin MeSH
- retinoid isomerohydrolase MeSH Browser
- Rhodopsin MeSH
- Carrier Proteins MeSH
Retinal disorders represent the main cause of decreased quality of vision and even blindness worldwide. The loss of retinal cells causes irreversible damage of the retina, and there are currently no effective treatment protocols for most retinal degenerative diseases. A promising approach for the treatment of retinal disorders is represented by stem cell-based therapy. The perspective candidates are mesenchymal stem cells (MSCs), which can differentiate into multiple cell types and produce a number of trophic and growth factors. In this study, we show the potential of murine bone marrow-derived MSCs to differentiate into cells expressing retinal markers and we identify the key supportive role of interferon-γ (IFN-γ) in the differentiation process. MSCs were cultured for 7 days with retinal extract and supernatant from T-cell mitogen concanavalin A-stimulated splenocytes, simulating the inflammatory site of retinal damage. MSCs cultured in such conditions differentiated to the cells expressing retinal cell markers such as rhodopsin, S antigen, retinaldehyde-binding protein, calbindin 2, recoverin, and retinal pigment epithelium 65. To identify a supportive molecule in the supernatants from activated spleen cells, MSCs were cultured with retinal extract in the presence of various T-cell cytokines. The expression of retinal markers was enhanced only in the presence of IFN-γ, and the supportive role of spleen cell supernatants was abrogated with the neutralization antibody anti-IFN-γ. In addition, differentiated MSCs were able to express a number of neurotrophic factors, which are important for retinal regeneration. Taken together, the results show that MSCs can differentiate into cells expressing retinal markers and that this differentiation process is supported by IFN-γ.
References provided by Crossref.org
The Immunomodulatory Potential of Mesenchymal Stem Cells in a Retinal Inflammatory Environment