Pesquisa e inovação biomédica avançada

Stem Cell Treatment of Chronic Radiation Cystitis in rats

Brossard Clement, Chapel A, Milliat F, Demarquay C, Buard V, Tarlet G, Squiban C, Linard C, Mathieu N, Dos Santos M, Granger R, Sache A, Denais Lalieve D

Introduction: Chronic Radiocystitis (CRC) is a consecutive pathology of pelvic irradiation characterized by 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 Stromal vascular fraction (SVF) 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 modelling of CRC in rats was implemented by localized irradiation guided by scanner imaging of the bladder
from 20 to 40 Gray with a follow-up of 3 to 6 months post-irradiation. Gene and protein expression analyses as well as histological and functional
parameters are carried out.


Results and Statistical Analysis: The analysis of urinary parameters revealed transient hematuria but no decrease in urinary volume over the 6
months. Transcriptomic analysis indicates a profile of chronic inflammation (IL1β, CCL2, IL6) and hypoxia (HIF1α) at 6 months. Histological
observations reveal a disorganization of urothelium at 6 months, with a decrease in its thickness and vascular lesions, which is consistent with gene
expression results.


Conclusion: These initial results attest to the relevance of the study by showing an initiation of CRC at 6 months with chronic inflammation, signs
of hypoxia, hematuria and urothelium disorganization. The analysis of kinetics over later times will make it possible to characterize the evolution
towards fibrosis and to have an established CRC. In a second step we will set up the treatment of this pathology by cell therapy.