Therapeutic mechanisms of mesenchymal stem cell derived exosomes in acute lung injury

doi:10.3969/j.issn.2095-4344.1815

Abstract

Abstract:

BACKGROUND: Exosomes are vesicles with phospholipid bilayers containing lots of proteins, lipid and RNA secreted by various types of cells, which might play important roles in cell-to-cell communication and signal transduction and participate in the regulation of important physiology or pathological processes. Recent studies have discovered that exosomes derived from mesenchymal stem cells, a promising treatment for acute lung injury, exert an anti-inflammation effect and improve the microvascular endothelial barrier permeability and enhance lung epithelial tissue repair.
OBJECTIVE: To review the recent advances in mesenchymal stem cells derived exosomes as a novel approach to the treatment of acute lung injury.
METHODS: Databases of PubMed and CNKI were searched for the articles related to the mechanism of mesenchymal stem cells-derived exosomes in the treatment of acute lung injury between 1981 and 2018. The keywords were “mesenchymal stem cells, exosomes, acute lung injury” in English and Chinese, respectively. Fifty-eight articles were enrolled for analysis.
RESULTS AND CONCLUSION: (1) Exosomes plays an important role in mediating intercellular communication and regulating immune system by transferring bioactive proteins, lipids and nucleic acids to target cells. (2) Mesenchymal stem cells-derived exosomes carry certain proteins, lipids, nucleic acids from mesenchymal stem cells. They might contribute to attenuating the inflammatory response and apoptosis, and promoting cell regeneration. (3) The existing researches summarize the main mechanism of treatment of acute lung injury by mesenchymal stem cell-derived exosomes, and provide reference for the future application of mesenchymal stem cell-derived exosomes in the treatment of acute lung injury.

Key words: exosomes, mesenchymal stem cells, acute lung injury, immunomodulation, apoptosis, cell regeneration, cell-free therapy, intercellular communication, National Natural Science Foundation of China

CLC Number:

Zhang Lishan, Zeng Mian. Therapeutic mechanisms of mesenchymal stem cell derived exosomes in acute lung injury[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(29): 4714-4721.

Figures/Tables 1

2.1 外泌体的概念与生物学特性外泌体首次被发现于20世纪80年代，Tram等[8-9]观察到网织红细胞在其成熟期间会分泌一种含有转铁蛋白受体的小囊泡，介导转铁蛋白受体的清除。然而在此后的十余年间外泌体并未受到研究人员的关注，仅被看作是细胞清除代谢废物的手段。直到20世纪90年代末，Zitvogel等[10]研究表明外泌体可能是细胞间通讯的重要介质，才重新激起了人们对外泌体研究的兴趣。研究证实了人体中几乎所有类型的细胞均能产生外泌体，且已经从多种体液中分离出外泌体，包括血液、尿液、唾液、精液、乳汁、胆汁、羊水、腹水和脑脊液等[11]。随后，一系列的研究发现许多细胞(包括免疫细胞、肠上皮细胞和间充质干细胞等)能通过释放外泌体来参与炎症反应、免疫反应和受损细胞增殖修复的调节[12-14]。外泌体是一种能被大多数细胞分泌的微小膜泡，具有脂质双层膜结构，见图2。根据国际细胞外囊泡学会的定义[15]，外泌体是细胞外囊泡(Extracellular vesicles)最小的亚组(细胞外囊泡3个亚组分别为：外泌体、微泡以及凋亡小体)，直径30-100 nm。细胞通过内吞作用形成早期内体(early endosome)，再与高尔基复合体相互作用以形成晚期内体，进而融合形成多泡体(MVBs，multivesicle bodies)，多泡体与质膜融合通过胞吐作用释放外泌体[16]，这个过程依赖于转运必需内体分选复合物(ESCRT)的作用。外泌体携带与细胞来源相关的多种蛋白质、脂质和核酸，能作为信号分子传递给其他细胞参与细胞活动的重要调控。虽然外泌体的形成过程大致相同，但不同细胞来源的外泌体在不同状态下所包含的内容物各不相同。目前已经被识别存在于外泌体的蛋白包括：膜联蛋白和flotillin(与外泌体的转运和融合有关)、四跨膜蛋白(参与细胞靶向)、Alix和TSG101(参与外泌体从多泡体的生物发生)、热休克蛋白(热休克蛋白60、热休克蛋白70和热休克蛋白90)、细胞外基质和细胞表面蛋白质(例如胶原蛋白、整联蛋白和半乳糖凝集素)、细胞表面受体(EGFR)等[17-18]。与其起源细胞相比，外泌体富含胆固醇、神经酰胺、磷酸甘油酯以及不饱和的脂肪酰基链，参与维持外泌体结构的稳定性[19]。此外，外泌体中的核酸是来源细胞核酸的一个子集，包括DNA、lncRNA、tRNA、mRNA、microRNA等。"

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