title: 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.
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France.
authors.forename: Lara
authors.initials: L
authors.lastname: Moussa
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Usunier
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Demarquay
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France.
authors.forename: Radia
authors.initials: R
authors.lastname: Tamarat
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sémont
authors.affiliation: Institut de Radioprotection et de SÛreté Nucléaire (IRSN), PRP-HOM/SRBE/LR2I, Fontenay-aux-Roses, France.
authors.forename: Noëlle
authors.initials: N
authors.lastname: Mathieu
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology / Q000528:radiation effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D064307:Microbiota; D018384:Oxidative Stress / Q000528:radiation effects; D011832:Radiation Injuries / Q000473:pathology* / Q000628:therapy; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: Bowel; Mesenchymal stromal cells (MSCs); Radiotherapy side effects; Regenerative medicine