Preclinical study of Chronic radiation cystitis and cell therapy treatment
Résumé
Introduction: Chronic radiocystitis (CRC) is a pathology resulting from irradiation of pelvic area without effective treatment. CRC is characterized by chronic inflammation leads to fibrosis. We investigated whether Mesenchymal Stromal Cells (MSC) treatment could reverse CRC damages.
Methods
Our study is divided into two parts, the modelling of CRC and the effect of treatment with MSCs. Preclinical CRC modelling in rats was performed by CT-guided localized irradiation of the bladder from 20 up to 80 Gy with a follow-up of 3 to 15 months after irradiation. Concerning MSCs treatment, bladder was irradiated at 40 Gy. Four month later, three intravenous injections, every two weeks, of 5.106 of MSCs was performed. A physiological, histological and molecular follow-up was done until 12 months post- irradiation.
Results: The transient haematuria increasing with time and irradiation dose. Transcriptomic analysis indicates an acute inflammation at 3 months (CCL2, CCL5, TNFα and IL1β upregulation). Results are in favour of tissue and vascular regeneration (EGF and VEGF upregulation) coupled with Extra Cellular Matrix (ECM) remodelling with overexpression of metalloprotease MMP2 and inhibitors, TIMP1/2/4, collagens Col1α2, Col3α1 and proteoglycan Cspg4.
At 6 months, a second wave of inflammation (CCL5, IL1β, IL6 and HIF1α upregulation) is observed, correlated with urothelium disorganization but without tissue and vascular regeneration or remodelling of the ECM.
Conclusion: Results have shown an initiation of CRC at 6 months, with chronic inflammation, hematuria, disorganization of the urothelium and fibrosis. Study is in progress to evaluate the efficacy of MSC treatment.
Domaines
Sciences du Vivant [q-bio]| Origine | Fichiers produits par l'(les) auteur(s) |
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