Bowel Radiation Injury: Complexity of the Pathophysiology and Promises of Cell and Tissue Engineering

Abstract

Ionizing radiation is effective to treat malignant pelvic cancers, but the toxicity to surrounding healthy tissue remains a substantial limitation. Early and late side effects not only limit the escalation of the radiation dose to the tumor but may also be life-threatening in some patients. Numerous preclinical studies determined specific mechanisms induced after irradiation in different compartments of the intestine. This review outlines the complexity of the pathogenesis, highlighting the roles of the epithelial barrier in the vascular network, and the inflammatory microenvironment, which together lead to chronic fibrosis. Despite the large number of pharmacological molecules available, the studies presented in this review provide encouraging proof of concept regarding the use of mesenchymal stromal cell (MSC) therapy to treat radiation-induced intestinal damage. The therapeutic efficacy of MSCs has been demonstrated in animal models and in patients, but an enormous number of cells and multiple injections are needed due to their poor engraftment capacity. Moreover, it has been observed that although MSCs have pleiotropic effects, some intestinal compartments are less restored after a high dose of irradiation. Future research should seek to optimize the efficacy of the injected cells, particularly with regard to extending their life span in the irradiated tissue. Moreover, improving the host microenvironment, combining MSCs with other specific regenerative cells, or introducing new tissue engineering strategies could be tested as methods to treat the severe side effects of pelvic radiotherapy.

Mesenchymal Stem Cell Administration Attenuates Colon Cancer Progression by Modulating the Immune Component within the Colorectal Tumor Microenvironment

“…The MNNG model is relevant for human carcinogenesis since rectal administration of MNNG mimic the detrimental action of alimentary nitroso‐compounds that are closely associated with the induction of CRC with a physiopathology similar to that observed in humans . Furthermore, intrarectal administration of MNNG act only on the colon mucosa in contrast to carcinogenesis induced by 1,2‐dimethylhydrazine or azoxymethane which also induce tumors in other tissues .…”

The Microbiome and Radiation Induced-Bowel Injury: Evidence for Potential Mechanistic Role in Disease Pathogenesis

“…Due to the lack of consensus about diagnostic criteria and an under-reporting of symptoms by patients, the true incidence of radiation-induced bowel injury is unknown. However, it is said that up to 90% of patients experience gastrointestinal symptoms in the first few weeks after receiving radiation to their abdominopelvic region [ 3 , 7 , 8 ]. There is also evidence to suggest that radiooncological inpatients have high incidence of Clostridium difficile infection with high mortality [ 9 ].…”

Prophylactic Faecalibacterium prausnitzii treatment prevents the acute breakdown of colonic epithelial barrier in a preclinical model of pelvic radiation disease

“…Colonic barrier disruption may drive bacterial translocation and likely the maintenance and/or exacerbation of mucosal inflammation. 2 After local radiation exposure, in the absence of acute immune response control, chronic inflammation could lead to persistent and irreversible damage. So, protecting the colonic mucosa from radiation toxicity and therefore from the progression of inflammation might result in the alleviation of acute and chronic side effects and should improve the patient's quality of life and/or reduce the risk of life-threatening conditions.…”