title: Use of mesenchymal stem cells (MSC) in chronic inflammatory fistulizing and fibrotic diseases: a comprehensive review.
abstract: Mesenchymal stem cells (MSC), multipotent adult stem cells, feature the potential to regenerate tissue damage and, in parallel, inhibit inflammation and fibrosis. MSC can be safely transplanted in autologous and allogeneic ways as they are non-immunogenic, and consequently represent a therapeutic option for refractory connective tissue diseases, fibrosing diseases like scleroderma and fistulizing colitis like in Crohn's disease. Actually, there are more than 200 registered clinical trial sites for evaluating MSC therapy, and 22 are on autoimmune diseases. In irradiation-induced colitis, MSC accelerate functional recovery of the intestine and dampen the systemic inflammatory response. In order to provide rescue therapy for accidentally over-irradiated prostate cancer patients who underwent radiotherapy, allogeneic bone marrow-derived MSC from family donors were intravenously infused to three patients with refractory and fistulizing colitis resembling fistulizing Crohn's disease. Systemic MSC therapy of refractory irradiation-induced colitis was safe and effective on pain, diarrhoea, hemorrhage, inflammation and fistulization accompanied by modulation of the lymphocyte subsets towards an increase of T regulatory cells and a decrease of activated effector T cells. The current data indicate that MSC represent a promising alternative strategy in the treatment of various immune-mediated diseases. Encouraging results have already been obtained from clinical trials in Crohn's disease and SLE as well as from case series in systemic sclerosis. MSC represent a safe therapeutic measure for patients who suffer from chronic and fistulizing colitis. These findings are instructional for the management of refractory inflammatory bowel diseases that are characterized by similar clinical and immunopathological features.
authors.affiliation: Department of Hematology, Saint Antoine Hospital APHP and UPMC University, UMRS 938, 184 rue Faubourg Saint Antoine, 75012, Paris, France, jan.voswinkel@sat.aphp.fr.
authors.forename: Jan
authors.initials: J
authors.lastname: Voswinkel
authors.forename: Sabine
authors.initials: S
authors.lastname: Francois
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Simon
authors.forename: Marc
authors.initials: M
authors.lastname: Benderitter
authors.forename: Norbert-Claude
authors.initials: NC
authors.lastname: Gorin
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.forename: Loïc
authors.initials: L
authors.lastname: Fouillard
authors.forename: Alain
authors.initials: A
authors.lastname: Chapel
mesh_terms: D000818:Animals; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D005355:Fibrosis / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007154:Immune System Diseases / Q000276:immunology / Q000628:therapy*; D007249:Inflammation / Q000276:immunology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D012003:Rectal Fistula / Q000276:immunology / Q000628:therapy*; D044968:Regenerative Medicine / Q000639:trends; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*