Effect of heme oxygenase‐1 transduced bone marrow mesenchymal stem cells on damaged intestinal epithelial cells in vitro

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 stabl...

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Published in:Cell biology international 2017-07, Vol.41 (7), p.726-738
Main Authors: Cao, Yi, Wu, Ben‐Juan, Zheng, Wei‐Ping, Yin, Ming‐Li, Liu, Tao, Song, Hong‐Li
Format: Article
Language:English
Subjects:
Animals
Bone marrow
Bone Marrow Cells - cytology
Bone Marrow Cells - enzymology
Bone Marrow Cells - metabolism
Caco-2 Cells
Cell Survival
Colon
Cytokines
Cytokines - metabolism
Epithelial cells
Epithelial Cells - cytology
Epithelial Cells - enzymology
Epithelial Cells - metabolism
Gene expression
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - enzymology
Hematopoietic Stem Cells - metabolism
Heme
Heme oxygenase (decyclizing)
Heme Oxygenase-1 - genetics
Heme Oxygenase-1 - metabolism
heme oxygenase‐1
Humans
Inflammation
Interleukin 10
Interleukin 2
Interleukin 6
Interleukins - metabolism
Intestinal Mucosa - cytology
Intestinal Mucosa - enzymology
Intestinal Mucosa - metabolism
intestinal mucosal barrier
Intestine
Maintenance
Male
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - enzymology
Mesenchymal Stromal Cells - metabolism
Mesenchyme
mRNA
Oxygenase
Rats
Rats, Wistar
Rodents
Stem cell transplantation
Stem cells
tight junction protein
Transduction, Genetic
Tumor necrosis factor
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-TNF
tumor necrosis factor‐α
zona occludens‐1
Zonula occludens-1 protein
Zonula Occludens-1 Protein - metabolism
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Summary: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.
ISSN:1065-6995
1095-8355
DOI:10.1002/cbin.10749