title: Protective effect of bone marrow mesenchymal stem cells in intestinal barrier permeability after heterotopic intestinal transplantation.
abstract: OBJECTIVE
  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-α (TNF-α), interferon-γ (INF-γ), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β) 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-α and INF-γ 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-β 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).
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Wen
authors: W
authors: Zhang
authors: 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.
authors: Zhong-Yang
authors: ZY
authors: Shen
authors: 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.
authors: Hong-Li
authors: HL
authors: Song
authors: 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.
authors: Yang
authors: Y
authors: Yang
authors: 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.
authors: Ben-Juan
authors: BJ
authors: Wu
authors: 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.
authors: Nan-Nan
authors: NN
authors: Fu
authors: 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.
authors: Tao
authors: T
authors: Liu
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006085:Graft Survival; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D007421:Intestine, Small / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D046529:Microscopy, Electron, Transmission; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D010539:Permeability; D012333:RNA, Messenger / Q000378:metabolism; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D016042:Transplantation, Heterotopic; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D062793:Occludin; C568987:Ocln protein, rat; D012333:RNA, Messenger; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D019344:Lactic Acid; D006631:Amine Oxidase (Copper-Containing)
keywords: Bone marrow mesenchymal stem cells; Intestinal mucosal barrier; Occludin; Small intestinal transplantation; Zona occludens-1