PMID- 24966614 OWN - NLM STAT- MEDLINE DCOM- 20150413 LR - 20211021 IS - 2219-2840 (Electronic) IS - 1007-9327 (Print) IS - 1007-9327 (Linking) VI - 20 IP - 23 DP - 2014 Jun 21 TI - Protective effect of bone marrow mesenchymal stem cells in intestinal barrier permeability after heterotopic intestinal transplantation. PG - 7442-51 LID - 10.3748/wjg.v20.i23.7442 [doi] AB - AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model. METHODS: BM MSCs were isolated from male Lewis rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. The HIT models were divided into a non-rejection group, saline-treated rejection group (via penile vein), and BM MSC-treated group (via penile vein). Intestinal mucosal barrier injury was estimated by diamine oxidase (DAO) and D-lactic acid (D-LA) expression levels. Tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (INF-gamma), interleukin-10 (IL-10), and transforming growth factor-beta (TGF-beta) were detected by enzyme-linked immunosorbent assay. Ultrastructural change of tight junctions (TJs) was observed under transmission electron microscope. Expression levels of the TJ proteins occludin and zona occludens (ZO)-1, affected by the inflammatory factors, were measured using real-time polymerase chain reaction and Western blotting. RESULTS: The pathological score at each time point after surgery indicated significantly less serious injury in the BM MSCs-treated group than in the rejection group (P < 0.05). In the former, graft levels of DAO and D-LA were reduced, and TNF-alpha and INF-gamma production was inhibited (at day 7: 10.6473 +/- 0.0710 vs 17.2128 +/- 0.4991, P < 0.05; 545.1506 +/- 31.9416 vs 810.2637 +/- 25.1175, P < 0.05). IL-10 and TGF-beta production was increased greatly (at day 7: 125.7773 +/- 4.7719 vs 80.3756 +/- 2.5866, P < 0.05; 234.5273 +/- 9.3980 vs 545.1506 +/- 31.9416, P < 0.05). There was increased expression of occludin and ZO-1 protein (at day 7: 0.2674 +/- 0.0128 vs 0.1352 +/- 0.0142, P < 0.05; at day 5: 0.7189 +/- 0.0289 vs 0.4556 +/- 0.0242, P < 0.05) and mRNA (at day 7: 0.3860 +/- 0.0254 vs 0.1673 +/- 0.0369, P < 0.05; at day 5: 0.5727 +/- 0.0419 vs 0.3598 +/- 0.0242, P < 0.05). CONCLUSION: BM MSCs can improve intestinal barrier permeability, repair TJs, and increase occludin and ZO-1 protein expression. With altered cytokine levels, they can protect the intestinal mucosa after transplantation. FAU - Zhang, Wen AU - Zhang W AD - Wen Zhang, Zhong-Yang Shen, Hong-Li Song, Yang Yang, Ben-Juan Wu, Nan-Nan Fu, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China. FAU - Shen, Zhong-Yang AU - Shen ZY AD - Wen Zhang, Zhong-Yang Shen, Hong-Li Song, Yang Yang, Ben-Juan Wu, Nan-Nan Fu, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China. FAU - Song, Hong-Li AU - Song HL AD - Wen Zhang, Zhong-Yang Shen, Hong-Li Song, Yang Yang, Ben-Juan Wu, Nan-Nan Fu, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China. FAU - Yang, Yang AU - Yang Y AD - Wen Zhang, Zhong-Yang Shen, Hong-Li Song, Yang Yang, Ben-Juan Wu, Nan-Nan Fu, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China. FAU - Wu, Ben-Juan AU - Wu BJ AD - Wen Zhang, Zhong-Yang Shen, Hong-Li Song, Yang Yang, Ben-Juan Wu, Nan-Nan Fu, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China. FAU - Fu, Nan-Nan AU - Fu NN AD - Wen Zhang, Zhong-Yang Shen, Hong-Li Song, Yang Yang, Ben-Juan Wu, Nan-Nan Fu, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China. FAU - Liu, Tao AU - Liu T AD - Wen Zhang, Zhong-Yang Shen, Hong-Li Song, Yang Yang, Ben-Juan Wu, Nan-Nan Fu, Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (Cytokines) RN - 0 (Inflammation Mediators) RN - 0 (Occludin) RN - 0 (Ocln protein, rat) RN - 0 (RNA, Messenger) RN - 0 (Tjp1 protein, rat) RN - 0 (Zonula Occludens-1 Protein) RN - 33X04XA5AT (Lactic Acid) RN - EC 1.4.3.21 (Amine Oxidase (Copper-Containing)) SB - IM MH - Amine Oxidase (Copper-Containing)/metabolism MH - Animals MH - *Bone Marrow Transplantation MH - Cells, Cultured MH - Cytokines/metabolism MH - Graft Survival MH - Inflammation Mediators/metabolism MH - Intestinal Mucosa/metabolism/*transplantation/ultrastructure MH - Intestine, Small/metabolism/*transplantation/ultrastructure MH - Lactic Acid/metabolism MH - Male MH - *Mesenchymal Stem Cell Transplantation MH - Microscopy, Electron, Transmission MH - Occludin/genetics/metabolism MH - Permeability MH - RNA, Messenger/metabolism MH - Rats, Inbred BN MH - Rats, Inbred Lew MH - Tight Junctions/metabolism/ultrastructure MH - Time Factors MH - Transplantation, Heterotopic MH - Zonula Occludens-1 Protein/genetics/metabolism PMC - PMC4064089 OTO - NOTNLM OT - Bone marrow mesenchymal stem cells OT - Intestinal mucosal barrier OT - Occludin OT - Small intestinal transplantation OT - Zona occludens-1 EDAT- 2014/06/27 06:00 MHDA- 2015/04/14 06:00 PMCR- 2014/06/21 CRDT- 2014/06/27 06:00 PHST- 2014/01/09 00:00 [received] PHST- 2014/03/11 00:00 [revised] PHST- 2014/04/21 00:00 [accepted] PHST- 2014/06/27 06:00 [entrez] PHST- 2014/06/27 06:00 [pubmed] PHST- 2015/04/14 06:00 [medline] PHST- 2014/06/21 00:00 [pmc-release] AID - 10.3748/wjg.v20.i23.7442 [doi] PST - ppublish SO - World J Gastroenterol. 2014 Jun 21;20(23):7442-51. doi: 10.3748/wjg.v20.i23.7442.