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