title: Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis.
abstract: Damage to the enteric nervous system (ENS) associated with intestinal inflammation may underlie persistent alterations to gut functions, suggesting that enteric neurons are viable targets for novel therapies. Mesenchymal stem cells (MSCs) offer therapeutic benefits for attenuation of neurodegenerative diseases by homing to areas of inflammation and exhibiting neuroprotective, anti-inflammatory, and immunomodulatory properties. In culture, MSCs release soluble bioactive factors promoting neuronal survival and suppressing inflammation suggesting that MSC-conditioned medium (CM) provides essential factors to repair damaged tissues. We investigated whether MSC and CM treatments administered by enema attenuate 2,4,6-trinitrobenzene-sulfonic acid (TNBS)-induced enteric neuropathy and motility dysfunction in the guinea pig colon. Guinea pigs were randomly assigned to experimental groups and received a single application of TNBS (30 mg/kg) followed by 1 × 10(6) human bone marrow-derived MSCs, 300 μl CM, or 300 μl unconditioned medium 3 h later. After 7 days, the effect of these treatments on enteric neurons was assessed by histological, immunohistochemical, and motility analyses. MSC and CM treatments prevented inflammation-associated weight loss and gross morphological damage in the colon; decreased the quantity of immune infiltrate in the colonic wall (P < 0.01) and at the level of the myenteric ganglia (P < 0.001); prevented loss of myenteric neurons (P < 0.05) and damage to nerve processes, changes in ChAT, and nNOS immunoreactivity (P < 0.05); and alleviated inflammation-induced colonic dysmotility (contraction speed; P < 0.001, contractions/min; P < 0.05). These results provide strong evidence that both MSC and CM treatments can effectively prevent damage to the ENS and alleviate gut dysfunction caused by TNBS-induced colitis.
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Australia;
authors.forename: Ainsley M
authors.initials: AM
authors.lastname: Robinson
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Australia;
authors.forename: Samy
authors.initials: S
authors.lastname: Sakkal
authors.affiliation: Department of Anatomy and Neuroscience, Monash University, Melbourne, Australia;
authors.forename: Anthony
authors.initials: A
authors.lastname: Park
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Australia;
authors.forename: Valentina
authors.initials: V
authors.lastname: Jovanovska
authors.affiliation: Department of Anatomy and Neuroscience, Monash University, Melbourne, Australia; Australian Regenerative Medicine Institute, Monash University, Melbourne, Australia; and.
authors.forename: Natalie
authors.initials: N
authors.lastname: Payne
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Australia;
authors.forename: Simona E
authors.initials: SE
authors.lastname: Carbone
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Australia;
authors.forename: Sarah
authors.initials: S
authors.lastname: Miller
authors.affiliation: Department of Physiology, Melbourne University, Melbourne, Australia.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Bornstein
authors.affiliation: Department of Anatomy and Neuroscience, Monash University, Melbourne, Australia; Australian Regenerative Medicine Institute, Monash University, Melbourne, Australia; and.
authors.forename: Claude
authors.initials: C
authors.lastname: Bernard
authors.affiliation: Department of Anatomy and Neuroscience, Monash University, Melbourne, Australia;
authors.forename: Richard
authors.initials: R
authors.lastname: Boyd
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Australia; kulmira.nurgali@vu.edu.au.
authors.forename: Kulmira
authors.initials: K
authors.lastname: Nurgali
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000473:pathology; D017077:Culture Media, Conditioned; D017615:Enteric Nervous System / Q000473:pathology*; D005260:Female; D005769:Gastrointestinal Motility; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D010523:Peripheral Nervous System Diseases / Q000517:prevention & control*; D014302:Trinitrobenzenesulfonic Acid; D015431:Weight Loss / Q000187:drug effects
chemical_list: D017077:Culture Media, Conditioned; D014302:Trinitrobenzenesulfonic Acid
keywords: colon motility; enteric neurons; inflammatory bowel disease; intestinal inflammation; mesenchymal stem cells