title: Effect of heme oxygenase-1 transduced bone marrow mesenchymal stem cells on damaged intestinal epithelial cells in vitro.
abstract: In this study, we explored the effects of mesenchymal stem cells (MSCs) from bone marrow overexpressing heme oxygenase-1 (HO-1) on the damaged human intestinal epithelial barrier in vitro. Rat MSCs were isolated from bone marrow and transduced with rat HO-1 recombinant adenovirus (HO-MSCs) for stable expression of HO-1. Colorectal adenocarinoma 2 (Caco2) cells were treated with tumor necrosis factor-α (TNF-α) to establish a damaged colon epithelial model. Damaged Caco2 were cocultured with MSCs, Ad-MSCs, Ad-HO + MSCs or HO-MSCs. mRNA and protein expression of Zona occludens-1 (ZO-1) and human HO-1 and the release of cytokines were measured. ZO-1 and human HO-1 in Caco2 were significantly decreased after treatment with TNF-α; and this effect was reduced when coculture with MSCs from bone marrow. Expression of ZO-1 was not significantly affected by Caco2 treatment with TNF-α, Ad-HO, and MSCs. In contrast, ZO-1 and human HO-1 increased significantly when the damaged Caco2 was treated with HO-MSCs. HO-MSCs showed the strongest effect on the expression of ZO-1 in colon epithelial cells. Coculture with HO-MSCs showed the most significant effects on reducing the expression of IL-2, IL-6, IFN-γ and increasing the expression of IL-10. HO-MSCs protected the intestinal epithelial barrier, in which endogenous HO-1 was involved. HO-MSCs play an important role in the repair process by reducing the release of inflammatory cytokines and increasing the release of anti-inflammatory factors. These results suggested that HO-MSCs from bone marrow were more effective in repairing the damaged intestinal epithelial barrier, and the effectiveness of MSCs was improved by HO-1 gene transduction, which provides favorable support for the application of stem cell therapy in the intestinal diseases.
authors.affiliation: Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Ben-Juan
authors.initials: BJ
authors.lastname: Wu
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zheng
authors.affiliation: Tianjin First Central Hospital Clinic Institute, Tianjin Medical University, Tianjin, China.
authors.forename: Ming-Li
authors.initials: ML
authors.lastname: Yin
authors.affiliation: Key Laboratory of Emergency Care Medicine of Ministry of Health, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.|Tianjin Key Laboratory of Organ Transplantation, Tianjin, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Song
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D018938:Caco-2 Cells; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D016207:Cytokines; D007378:Interleukins; C569044:Tjp1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D051547:Heme Oxygenase-1
keywords: heme oxygenase-1; intestinal mucosal barrier; mesenchymal stem cells; tight junction protein; tumor necrosis factor-α; zona occludens-1