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Article

HGF and TSG-6 Released by Mesenchymal Stem Cells Attenuate Colon Radiation-Induced Fibrosis

Service de Recherche en Radiobiologie et en Médecine Régénérative (SERAMED), Laboratoire de Radiobiologie des Expositions Médicales (LRMED), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Fontenay-aux-Roses, F-92260 Paris, France
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Int. J. Mol. Sci. 2021, 22(4), 1790; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041790
Received: 16 December 2020 / Revised: 27 January 2021 / Accepted: 5 February 2021 / Published: 11 February 2021
Fibrosis is a leading cause of death in occidental states. The increasing number of patients with fibrosis requires innovative approaches. Despite the proven beneficial effects of mesenchymal stem cell (MSC) therapy on fibrosis, there is little evidence of their anti-fibrotic effects in colorectal fibrosis. The ability of MSCs to reduce radiation-induced colorectal fibrosis has been studied in vivo in Sprague–Dawley rats. After local radiation exposure, rats were injected with MSCs before an initiation of fibrosis. MSCs mediated a downregulation of fibrogenesis by a control of extra cellular matrix (ECM) turnover. For a better understanding of the mechanisms, we used an in vitro model of irradiated cocultured colorectal fibrosis in the presence of human MSCs. Pro-fibrotic cells in the colon are mainly intestinal fibroblasts and smooth muscle cells. Intestinal fibroblasts and smooth muscle cells were irradiated and cocultured in the presence of unirradiated MSCs. MSCs mediated a decrease in profibrotic gene expression and proteins secretion. Silencing hepatocyte growth factor (HGF) and tumor necrosis factor-stimulated gene 6 (TSG-6) in MSCs confirmed the complementary effects of these two genes. HGF and TSG-6 limited the progression of fibrosis by reducing activation of the smooth muscle cells and myofibroblast. To settle in vivo the contribution of HGF and TSG-6 in MSC-antifibrotic effects, rats were treated with MSCs silenced for HGF or TSG-6. HGF and TSG-6 silencing in transplanted MSCs resulted in a significant increase in ECM deposition in colon. These results emphasize the potential of MSCs to influence the pathophysiology of fibrosis-related diseases, which represent a challenging area for innovative treatments. View Full-Text
Keywords: mesenchymal stem cells; colorectal; cancer; fibrosis; radiotherapy; inflammation; fibrosis; HGF; TSG-6 mesenchymal stem cells; colorectal; cancer; fibrosis; radiotherapy; inflammation; fibrosis; HGF; TSG-6
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MDPI and ACS Style

Usunier, B.; Brossard, C.; L’Homme, B.; Linard, C.; Benderitter, M.; Milliat, F.; Chapel, A. HGF and TSG-6 Released by Mesenchymal Stem Cells Attenuate Colon Radiation-Induced Fibrosis. Int. J. Mol. Sci. 2021, 22, 1790. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041790

AMA Style

Usunier B, Brossard C, L’Homme B, Linard C, Benderitter M, Milliat F, Chapel A. HGF and TSG-6 Released by Mesenchymal Stem Cells Attenuate Colon Radiation-Induced Fibrosis. International Journal of Molecular Sciences. 2021; 22(4):1790. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041790

Chicago/Turabian Style

Usunier, Benoît; Brossard, Clément; L’Homme, Bruno; Linard, Christine; Benderitter, Marc; Milliat, Fabien; Chapel, Alain. 2021. "HGF and TSG-6 Released by Mesenchymal Stem Cells Attenuate Colon Radiation-Induced Fibrosis" Int. J. Mol. Sci. 22, no. 4: 1790. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22041790

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