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鸡骨髓间充质干细胞可改善肺及远隔器官损伤。

Chicken bone marrow mesenchymal stem cells improve lung and distal organ injury.

机构信息

Harbin Sport University, Harbin, 150008, People's Republic of China.

Department of Animal Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences, 2 Yuanmingyuan Road, Beijing, 100193, People's Republic of China.

出版信息

Sci Rep. 2021 Sep 10;11(1):17937. doi: 10.1038/s41598-021-97383-4.

Abstract

Mesenchymal stem cells (MSCs) are associated with pulmonary protection and longevity. We separated chicken bone marrow-derived mesenchymal stem cells (BM-MSCs); investigated whether BM-MSCs can improve lipopolysaccharide (LPS)-induced lung and distal organ injury; and explored the underlying mechanisms. Ninety-six male ICR (6 weeks old) mice were randomly divided into three groups: Sham, LPS, and LPS + MSC groups. The mice were intratracheally injected with 5 mg/kg LPS to induce acute lung injury (ALI). The histopathological severity of injury to the lung, liver, kidney, heart, and aortic tissues was detected. Wet/dry ratio, protein concentrations in bronchoalveolar lavage fluid (BALF), BALF cell counts, inflammatory cytokine levels in serum, inflammatory cytokine gene expression, and oxidative stress-related indicators were detected. In addition, a survival analysis was performed in sixty male ICR mice (6 weeks old, 18-20 g). This study used chicken BM-MSCs, which are easier to obtain and more convenient than other animal or human MSCs, and have MSC-associated properties, such as a colony forming ability, multilineage differentiation potential, and certain phenotypes. BM-MSCs administration significantly improved the survival rate, systemic inflammation, and the histopathological severity of lung, liver, kidney, and aortic injury during ALI. BM-MSCs administration reduced the levels of inflammatory factors in BALF, the infiltration of neutrophils, and oxidative stress injury in lung tissue. In addition, BM-MSCs administration reduced TRL4 and Mdy88 mRNA expression during ALI. Chicken BM-MSCs serve as a potential alternative resource for stem cell therapy and exert a prominent effect on LPS-induced ALI and extrapulmonary injury, in part through TRL4/Mdy88 signaling and inhibition of neutrophil inflammation and oxidative stress injury.

摘要

间质干细胞(MSCs)与肺保护和长寿有关。我们分离了鸡骨髓源性间充质干细胞(BM-MSCs);研究了 BM-MSCs 是否可以改善脂多糖(LPS)诱导的肺和远隔器官损伤;并探讨了潜在的机制。96 只雄性 ICR(6 周龄)小鼠随机分为三组:Sham、LPS 和 LPS+MSC 组。通过气管内注射 5mg/kg LPS 诱导急性肺损伤(ALI)。检测肺、肝、肾、心和主动脉组织损伤的组织病理学严重程度。检测湿/干比、支气管肺泡灌洗液(BALF)中的蛋白浓度、BALF 细胞计数、血清中炎症细胞因子水平、炎症细胞因子基因表达和氧化应激相关指标。此外,对 60 只雄性 ICR 小鼠(6 周龄,18-20g)进行了生存分析。本研究使用鸡 BM-MSCs,其比其他动物或人类 MSCs 更容易获得且更方便,并且具有 MSC 相关特性,如集落形成能力、多能性分化潜能和某些表型。BM-MSCs 给药显著提高了 ALI 期间的存活率、全身炎症反应以及肺、肝、肾和主动脉损伤的组织病理学严重程度。BM-MSCs 给药降低了 BALF 中的炎症因子水平、中性粒细胞浸润和肺组织的氧化应激损伤。此外,BM-MSCs 给药降低了 ALI 期间 TRL4 和 Mdy88 mRNA 的表达。鸡 BM-MSCs 可作为干细胞治疗的潜在替代资源,对 LPS 诱导的 ALI 和远隔器官损伤具有显著作用,部分通过 TRL4/Mdy88 信号通路以及抑制中性粒细胞炎症和氧化应激损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976c/8433226/72df258083af/41598_2021_97383_Fig1_HTML.jpg

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