Mesenchymal stem cells and conditioned medium avert enteric neuropathy and colon dysfunction in guinea pig TNBS-induced colitis

Background Aims: 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. Methods: Guinea-pigs were randomly assigned to experimental groups and received a single application of TNBS (30mg/kg) followed by 1x106 human bone marrow-derived MSCs, 300microL CM, or 300microL unconditioned medium (UCM) 3 hours later. After 7 days, the effect of these treatments on enteric neurons was assessed by histological, immunohistochemical, and motility analyses. Results: 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