Cellular therapy treatment of chronic radiation cystitis in rats
Résumé
Introduction and aim of the study: Chronic Radiocystitis (CRC) is a pathology resulting from radiation to the pelvic area. It is characterized by a chronic inflammation, sometimes progressing to fibrosis and in the most severe cases to fistulas with symptoms such as pain and bleeding. There is no effective treatment and we propose to test mesenchymal stem cells (MSC) as a new therapeutic method. Our previous studies on radiation rectitis have shown that MSCs can reverse chronic inflammation and fibrosis after irradiation. Material and Methods: Preclinical modeling of CRC in rats was performed by localized irradiation guided by 20 to 40 Gray bladder CT imaging with 3 to 6 months post-irradiation follow-up. Analyses of gene and protein expression as well as histological and functional parameters were performed.
Results and Statistical Analysis: The analysis of the urinary parameters allowed to highlight transient hematuria but no decrease of the urinary volume during the 6 months. Transcriptomic analysis indicates a profile in favor of chronic inflammation (IL1β, CCL2, IL6) and hypoxia (HIF1α) at 6 months but no pro-fibrotic profile (αSMA). Histological observations reveal a disorganization of the urothelium at 6 months, with a decrease in its thickness and vascular lesions but no fibrosis, which is consistent with the gene expression results.
Conclusion: These first results confirm the relevance of the study by showing an initiation of CRC at 6 months with chronic inflammation, signs of hypoxia, hematuria and urothelium disorganization, without decrease in urinary volume. Analysis of the kinetics over later time periods will allow characterizing the progression to fibrosis and to have an established CRC. In a second step we will set up the treatment of this pathology by CSM.
Domaines
Sciences du Vivant [q-bio]Origine | Fichiers produits par l'(les) auteur(s) |
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