Antiapoptotic Properties of Mesenchymal Stem Cells in a Mouse Model of Corneal Inflammation
| Autor: | Jan Kossl, Vladimir Holan, Eliska Javorkova, Barbora Hermankova, Pavla Bohacova, Alena Zajicova |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Population Apoptosis Biology Mesenchymal Stem Cell Transplantation Corneal inflammation Proinflammatory cytokine Cornea 03 medical and health sciences 0302 clinical medicine Animals Humans Limbal stem cell education Cells Cultured Keratitis Mice Inbred BALB C education.field_of_study Hepatocyte Growth Factor Reverse Transcriptase Polymerase Chain Reaction Regeneration (biology) Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology Hematology Cell biology Transplantation Disease Models Animal 030104 developmental biology Gene Expression Regulation Cyclooxygenase 2 Cytokines Female sense organs 030217 neurology & neurosurgery Corneal Injuries Developmental Biology Adult stem cell |
| Zdroj: | Stem Cells and Development. 30:418-427 |
| ISSN: | 1557-8534 1547-3287 |
| Popis: | Mesenchymal stem cells (MSCs) represent a population of adult stem cells that have potent immunoregulatory, anti-inflammatory, and antiapoptotic properties. In addition, they have ability to migrate to the site of inflammation or injury, where they contribute to the regeneration and healing process. For these properties, MSCs have been used as therapeutic cells in several models, including treatment of damages or disorders of the ocular surface. If the damage of the ocular surface is extensive and involves a limbal region where limbal stem cell reside, MSC therapy has been proved as the effective treatment approach. Although the anti-inflammatory properties of MSCs have been well characterized, mechanisms of antiapoptotic action of MSCs are not well recognized. Using a chemically damaged cornea in a mouse model, we showed that the injury decreases expression of the gene for antiapoptotic molecule Bcl-2 and increases the expression of proapoptotic genes Bax and p53. These changes were attenuated by local transplantation of MSCs after corneal damage. The antiapoptotic effect of MSCs was tested in an in vitro model of co-cultivation of corneal explants with MSCs. The apoptosis of corneal cells in the explants was induced by proinflammatory cytokines and was significantly inhibited in the presence of MSCs. The antiapoptotic effect of MSCs was mediated by paracrine action, as confirmed by separation of the explants in inserts or by supernatants from MSCs. In addition, MSCs decreased the expression of genes for the molecules associated with endoplasmic reticulum stress Atf4, Bip, and p21, which are associated with apoptosis. The results show that MSCs inhibit the expression of proapoptotic genes and decrease the number of apoptotic cells in the damaged corneas, and this action might be one of the mechanisms of the therapeutic action of MSCs. |
| Databáze: | OpenAIRE |
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