title: Mesenchymal stem cells increase self-renewal of small intestinal epithelium and accelerate structural recovery after radiation injury.
abstract: Patients who undergo pelvic or abdominal radiotherapy may develop side effects that can be life threatening. Tissue complications caused by radiation-induced stem cell depletion may result in structural and functional alterations of the gastrointestinal (GI) tract. Stem cell therapy using mesenchymal stem cells (MSC) is a promising approach for replenishment of the depleted stem cell compartment during radiotherapy. There is little information on the therapeutic potential of MSC in injured-GI tract following radiation exposure. In this study, we addressed the ability of MSC to support the structural regeneration of the small intestine after abdominal irradiation. We isolated MSC from human bone marrow and human mesenchymal stem cells (hMSC) were transplanted into immunotolerent NOD/SCID mice with a dose of 5.10(6) cells via the systemic route. Using a model of radiation-induced intestinal injury, we studied the link between damage, hMSC engraftment and the capacity of hMSC to sustain structural recovery. Tissue injury was assessed by histological analysis. hMSC engraftment in tissues was quantified by PCR assay. Following abdominal irradiation, the histological analysis of small intestinal structure confirms the presence of partial and transient (three days) mucosal atrophy. PCR analysis evidences a low but significant hMSC implantation in small intestine (0.17%) but also at all the sites of local irradiation (kidney, stomach and spleen). Finally, in presence of hMSC, the small intestinal structure is already recovered at three days after abdominal radiation exposure. We show a structural recovery accompanied by an increase of small intestinal villus height, three and fifteen days following abdominal radiation exposure. In this study, we show that radiation-induced small intestinal injury may play a role in the recruitment of MSC for the improvement of tissue recovery. This work supports, the use of MSC infusion to repair damaged GI tract in patients subjected to radiotherapy. MSC therapy to avoid extended intestinal crypt sterilization is a promising approach to diminish healthy tissue alterations during the course of pelvic radiotherapy.
authors.affiliation: UPRES 1638, IRSN, Fontenay aux Roses, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Sémont
authors.forename: Sabine
authors.initials: S
authors.lastname: François
authors.forename: Moubarak
authors.initials: M
authors.lastname: Mouiseddine
authors.forename: Agnès
authors.initials: A
authors.lastname: François
authors.forename: Amandine
authors.initials: A
authors.lastname: Saché
authors.forename: Johanna
authors.initials: J
authors.lastname: Frick
authors.forename: Dominique
authors.initials: D
authors.lastname: Thierry
authors.forename: Alain
authors.initials: A
authors.lastname: Chapel
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology* / Q000528:radiation effects; D006801:Humans; D007421:Intestine, Small / Q000166:cytology* / Q000473:pathology / Q000528:radiation effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011833:Radiation Injuries, Experimental; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000379:methods