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研究肺驻留、骨髓和胎盘来源的间充质干细胞治疗脂多糖诱导的急性肺损伤。

Study of mesenchymal stem cells derived from lung-resident, bone marrow and chorion for treatment of LPS-induced acute lung injury.

机构信息

Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

Department of Pulmonary Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Respir Physiol Neurobiol. 2022 Aug;302:103914. doi: 10.1016/j.resp.2022.103914. Epub 2022 Apr 18.

Abstract

BACKGROUND

Mesenchymal stem cells (MSCs) have been shown to improve acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). However, the optimal source of MSCs for cell-based therapy remains unknown. To determine which kind of MSCs are more effective, we compared the effects of rat lung resident MSC (LRMSC), human chorion-derived MSC (HMSC-C) and human bone marrow derived MSC (HMSC-BM) in LPS-induced ALI in mice.

METHODS

LPS (Pseudomonas aeruginosa) was used to induce ALI model. All three kinds of MSCs were administered via tail vein 4 h after LPS instillation. The mice were sacrificed 48 h after LPS instillation. H&E staining of lung section, wet-to-dry weight ratio of lung tissue, ratio of regulatory T cells (Tregs) and Th17 cells, and total protein concentration, leukocytes counting and cytokines in bronchoalveolar lavage fluid (BALF) were evaluated.

RESULTS

The data showed that compared with LRMSC and HMSC-BM, HMSC-C more significantly attenuated lung injury, upregulated the Tregs/Th17 cells ratio, and inhibited release of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and recruitment of neutrophils and macrophages into alveolus.

CONCLUSIONS

Although all three kinds of LRMSC, HMSC-C and HMSC-BM are protective against LPS-induced lung injury, HMSC-C was more effective than LRMSC and HMSC-BM to treat LPS-induced lung injury.

摘要

背景

间充质干细胞(MSCs)已被证明可改善急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)。然而,用于细胞治疗的最佳 MSC 来源仍不清楚。为了确定哪种 MSC 更有效,我们比较了 LPS 诱导的小鼠 ALI 模型中大鼠肺固有 MSC(LRMSC)、人绒毛膜来源 MSC(HMSC-C)和人骨髓来源 MSC(HMSC-BM)的作用。

方法

用 LPS(铜绿假单胞菌)诱导 ALI 模型。在 LPS 滴注后 4 小时通过尾静脉给予这三种 MSC。在 LPS 滴注后 48 小时处死小鼠。对肺组织切片进行 H&E 染色、肺组织湿重/干重比、调节性 T 细胞(Tregs)和 Th17 细胞的比值以及支气管肺泡灌洗液(BALF)中的总蛋白浓度、白细胞计数和细胞因子进行评估。

结果

数据显示,与 LRMSC 和 HMSC-BM 相比,HMSC-C 更显著地减轻了肺损伤,上调了 Tregs/Th17 细胞的比值,并抑制了炎症细胞因子(IL-1β、IL-6 和 TNF-α)的释放以及中性粒细胞和巨噬细胞向肺泡的募集。

结论

尽管三种 LRMSC、HMSC-C 和 HMSC-BM 均对 LPS 诱导的肺损伤具有保护作用,但与 LRMSC 和 HMSC-BM 相比,HMSC-C 对 LPS 诱导的肺损伤的治疗效果更显著。

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