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静脉注射脂肪来源干细胞移植对博来霉素诱导的间质性肺炎小鼠模型的抗炎和抗纤维化作用。

Anti-inflammatory and anti-fibrotic effects of intravenous adipose-derived stem cell transplantation in a mouse model of bleomycin-induced interstitial pneumonia.

机构信息

Department of Internal Medicine (IV), Osaka Medical College, Osaka, Japan.

Division of Central Laboratory, Osaka Medical College, Osaka, Japan.

出版信息

Sci Rep. 2017 Nov 6;7(1):14608. doi: 10.1038/s41598-017-15022-3.

DOI:10.1038/s41598-017-15022-3
PMID:29097816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5668313/
Abstract

Adipose-derived stem cells (AdSCs) have recently been considered a useful treatment tool for autoimmune disease because of their anti-inflammatory and immunosuppressive effects. We investigated the therapeutic effect of intravenous AdSC transplantation in a mouse model of bleomycin-induced lung injury. AdSCs accumulated in the pulmonary interstitium and inhibited both inflammation and fibrosis in the lung, markedly improving the survival rate of mice with bleomycin-induced lung injury in a cell number-dependent manner. AdSCs inhibited the production of pro-inflammatory cytokines such as TNF-α and IL-12 in activated macrophages, and AdSCs also induced the apoptosis of activated macrophages. AdSCs inhibited the differentiation and proliferation of Th2-type mCD4+ T cells but promoted the differentiation and proliferation of regulatory T cells, suggesting that the phenotypic conversion of T cells may be one of the mechanisms for the anti-inflammatory effect of AdSCs on pulmonary fibrosis. These findings suggest that intravenous AdSCs could be a promising treatment for patients with interstitial pneumonia.

摘要

脂肪来源干细胞(AdSCs)因其具有抗炎和免疫抑制作用,最近被认为是一种治疗自身免疫性疾病的有用工具。我们研究了静脉注射 AdSC 移植在博来霉素诱导的肺损伤小鼠模型中的治疗效果。AdSCs 聚集在肺间质中,抑制肺部炎症和纤维化,以细胞数量依赖的方式显著提高博来霉素诱导的肺损伤小鼠的存活率。AdSCs 抑制了活化巨噬细胞中促炎细胞因子如 TNF-α和 IL-12 的产生,并且 AdSCs 还诱导了活化巨噬细胞的凋亡。AdSCs 抑制了 Th2 型 mCD4+T 细胞的分化和增殖,但促进了调节性 T 细胞的分化和增殖,这表明 T 细胞的表型转化可能是 AdSCs 对肺纤维化抗炎作用的机制之一。这些发现表明,静脉注射 AdSCs 可能是治疗间质性肺炎患者的一种有前途的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/de9066c032b7/41598_2017_15022_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/d118b8138217/41598_2017_15022_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/cb8f858f00dc/41598_2017_15022_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/75b73f64e5ac/41598_2017_15022_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/63b651c4a3af/41598_2017_15022_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/c9fd81ed1e5b/41598_2017_15022_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/de9066c032b7/41598_2017_15022_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/d118b8138217/41598_2017_15022_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/cb8f858f00dc/41598_2017_15022_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/75b73f64e5ac/41598_2017_15022_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/63b651c4a3af/41598_2017_15022_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/c9fd81ed1e5b/41598_2017_15022_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d941/5668313/de9066c032b7/41598_2017_15022_Fig6_HTML.jpg

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