Abstract (AI)
Introduction: Mesenchymal stem cells (MSCs) have been reported to be a valuable cell source in regenerative medicine, and bone marrow represents a major source of MSCs.Recently, it has been shown that MSC can be easily isolated from human amnion, which is generally discarded after delivery, and a large amount of cells can be obtained.We have previously reported that intravenous administration of human amnion-derived MSCs (hAMSCs) provided significant improvement in rats with colitis induced by dextran sulfate sodium or girradiation.In addition, conditioned medium (CM) obtained from MSCs contains a variety of humoral factors to improve damaged tissues.In this study, we investigated the effects of hAMSCs and CM in rats with 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis.Aims & Methods: hAMSCs were isolated and expanded by digestion with collagenase, followed by culturing in uncoated plastic dishes.CM was collected by culturing subconfluent hAMSCs with serum-free MEMa for 48 hrs.CM gel was prepared by mixing CM with 2% carboxymethyl cellulose.On day 0, 200 l of TNBS (15 mg/rat) in 30% ethanol was intrarectally administered to the ten-week-old male Sprague-Dawley (SD) rats.One-million hAMSCs were intravenously administered 3 hrs after TNBS treatment, and rats were sacrificed on day 7 for histological examination and quantitative PCR.In another experiment, 400 l of CM gel was intrarectally administered 3 hrs after TNBS treatment, and day 1 and day 2. Results: hAMSC transplantation and CM gel enema significantly improved the endoscopical score, and tended to improve the histological score.Quantitative PCR demonstrated that the expression levels of TNF-, CXCL1 and CCL2 tended to be decreased by hAMSC transplantation and CM gel enema.Infiltrations of CD68-positive macrophages and myeloperoxidase-positive neutrophils were significantly decreased by hAMSC transplantation and CM gel enema.Conclusion: Transplantation of hAMSCs and CM gel enema provided significant improvement in rats with colitis induced by TNBS.hAMSCs or CM from hAMSCs may be new therapeutic strategies inflammatory bowel disease.
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2016-10-01
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