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血红素加氧酶-1转导的骨髓间充质干细胞对减轻大鼠急性排斥反应及改善小肠移植结局的作用

Heme oxygenase-1-transduced bone marrow mesenchymal stem cells in reducing acute rejection and improving small bowel transplantation outcomes in rats.

作者信息

Yang Yang, Song Hong Li, Zhang Wen, Wu Ben Juan, Fu Nan Nan, Dong Chong, Shen Zhong Yang

机构信息

Department of Organ Transplantation, Tianjin First Central Hospital, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.

Tianjin Key Laboratory of Organ Transplantation, 24# Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.

出版信息

Stem Cell Res Ther. 2016 Nov 20;7(1):164. doi: 10.1186/s13287-016-0427-8.

DOI:10.1186/s13287-016-0427-8
PMID:27866474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5116370/
Abstract

BACKGROUND

We determined whether bone marrow mesenchymal stem cells (BMMSCs) transduced with heme oxygenase-1 (HO-1), a cytoprotective and immune-protective factor, could improve outcomes for small bowel transplantation (SBTx) in rats.

METHODS

We performed heterotopic SBTx from Brown Norway rats to Lewis rats, before infusing Ad/HO-1-transduced BMMSCs (Ad/HO-1/BMMSCs) through the superficial dorsal veins of the penis. Respective infusions with Ad/BMMSCs, BMMSCs, and normal saline served as controls. The animals were sacrificed after 1, 5, 7, or 10 days. At each time point, we measured small bowel histology and apoptosis, HO-1 protein and mRNA expression, natural killer (NK) cell activity, cytokine concentrations in serum and intestinal graft, and levels of regulatory T (Treg) cells.

RESULTS

The saline-treated control group showed aggravated acute cellular rejection over time, with mucosal destruction, increased apoptosis, NK cell activation, and upregulation of proinflammatory and immune-related mediators. Both the Ad/BMMSC-treated group and the BMMSC-treated group exhibited attenuated acute cellular rejection at an early stage, but the effects receded 7 days after transplantation. Strikingly, the Ad/HO-1/BMMSC-treated group demonstrated significantly attenuated acute cellular rejection, reduced apoptosis and NK cell activity, and suppressed concentrations of inflammation and immune-related cytokines, and upregulated expression of anti-inflammatory cytokine mediators and increased Treg cell levels.

CONCLUSION

Our data suggest that Ad/HO-1-transduced BMMSCs have a reinforced effect on reducing acute rejection and protecting the outcome of SBTx in rats.

摘要

背景

我们确定了用血红素加氧酶-1（HO-1）转导的骨髓间充质干细胞（BMMSCs），一种具有细胞保护和免疫保护作用的因子，是否能改善大鼠小肠移植（SBTx）的结局。

方法

我们将棕色挪威大鼠的小肠异位移植到Lewis大鼠体内，然后通过阴茎背浅静脉输注Ad/HO-1转导的BMMSCs（Ad/HO-1/BMMSCs）。分别输注Ad/BMMSCs、BMMSCs和生理盐水作为对照。在1、5、7或10天后处死动物。在每个时间点，我们测量小肠组织学和细胞凋亡、HO-1蛋白和mRNA表达、自然杀伤（NK）细胞活性、血清和肠道移植物中的细胞因子浓度以及调节性T（Treg）细胞水平。

结果

生理盐水处理的对照组随着时间的推移急性细胞排斥反应加重，出现黏膜破坏、细胞凋亡增加、NK细胞活化以及促炎和免疫相关介质上调。Ad/BMMSC处理组和BMMSC处理组在早期均表现出急性细胞排斥反应减轻，但移植后7天效果消退。令人惊讶的是，Ad/HO-1/BMMSC处理组的急性细胞排斥反应明显减轻，细胞凋亡和NK细胞活性降低，炎症和免疫相关细胞因子浓度受到抑制，抗炎细胞因子介质表达上调，Treg细胞水平增加。

结论

我们的数据表明，Ad/HO-1转导的BMMSCs对减轻大鼠急性排斥反应和保护SBTx结局具有增强作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/18520ded247d/13287_2016_427_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/43aaeec343f3/13287_2016_427_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/fe180be4f526/13287_2016_427_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/300ad7f82491/13287_2016_427_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/518c94984e78/13287_2016_427_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/a10414a5f44d/13287_2016_427_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/8caf5cca7639/13287_2016_427_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/5f0cbfe4421d/13287_2016_427_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/565b30b34f7c/13287_2016_427_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/18520ded247d/13287_2016_427_Fig10_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/43aaeec343f3/13287_2016_427_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/fc0125e302a9/13287_2016_427_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/fe180be4f526/13287_2016_427_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/300ad7f82491/13287_2016_427_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/518c94984e78/13287_2016_427_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/a10414a5f44d/13287_2016_427_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/8caf5cca7639/13287_2016_427_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/5f0cbfe4421d/13287_2016_427_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/565b30b34f7c/13287_2016_427_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62bb/5116370/18520ded247d/13287_2016_427_Fig10_HTML.jpg

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