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无细胞方法的范式转变:MSC 衍生的外泌体在再生医学中的新兴作用。

A paradigm shift in cell-free approach: the emerging role of MSCs-derived exosomes in regenerative medicine.

机构信息

Department of Biochemistry and Molecular Biology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

DS & CI Research Group, Universitas Sumatera Utara, Medan, Indonesia.

出版信息

J Transl Med. 2021 Jul 12;19(1):302. doi: 10.1186/s12967-021-02980-6.


DOI:10.1186/s12967-021-02980-6
PMID:34253242
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8273572/
Abstract

Recently, mesenchymal stem/stromal cells (MSCs) due to their pro-angiogenic, anti-apoptotic, and immunoregulatory competencies along with fewer ethical issues are presented as a rational strategy for regenerative medicine. Current reports have signified that the pleiotropic effects of MSCs are not related to their differentiation potentials, but rather are exerted through the release of soluble paracrine molecules. Being nano-sized, non-toxic, biocompatible, barely immunogenic, and owning targeting capability and organotropism, exosomes are considered nanocarriers for their possible use in diagnosis and therapy. Exosomes convey functional molecules such as long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs), proteins (e.g., chemokine and cytokine), and lipids from MSCs to the target cells. They participate in intercellular interaction procedures and enable the repair of damaged or diseased tissues and organs. Findings have evidenced that exosomes alone are liable for the beneficial influences of MSCs in a myriad of experimental models, suggesting that MSC- exosomes can be utilized to establish a novel cell-free therapeutic strategy for the treatment of varied human disorders, encompassing myocardial infarction (MI), CNS-related disorders, musculoskeletal disorders (e.g. arthritis), kidney diseases, liver diseases, lung diseases, as well as cutaneous wounds. Importantly, compared with MSCs, MSC- exosomes serve more steady entities and reduced safety risks concerning the injection of live cells, such as microvasculature occlusion risk. In the current review, we will discuss the therapeutic potential of MSC- exosomes as an innovative approach in the context of regenerative medicine and highlight the recent knowledge on MSC- exosomes in translational medicine, focusing on in vivo researches.

摘要

最近,间充质干细胞(MSCs)由于其促血管生成、抗细胞凋亡和免疫调节能力,以及较少的伦理问题,被提出作为再生医学的一种合理策略。目前的报告表明,MSCs 的多效性效应与其分化潜能无关,而是通过释放可溶性旁分泌分子发挥作用。外泌体纳米大小、无毒、生物相容性好、免疫原性低,具有靶向能力和器官趋向性,被认为是用于诊断和治疗的纳米载体。外泌体传递功能性分子,如长非编码 RNA(lncRNA)和 microRNA(miRNA)、蛋白质(如趋化因子和细胞因子)和脂质,从 MSCs 传递到靶细胞。它们参与细胞间相互作用过程,使受损或患病的组织和器官得到修复。研究结果表明,外泌体本身是 MSCs 在众多实验模型中产生有益影响的原因,这表明 MSC-外泌体可用于建立一种新型的无细胞治疗策略,以治疗各种人类疾病,包括心肌梗死(MI)、中枢神经系统相关疾病、肌肉骨骼疾病(如关节炎)、肾脏疾病、肝脏疾病、肺部疾病以及皮肤伤口。重要的是,与 MSCs 相比,MSC-外泌体作为再生医学领域的一种创新方法,具有更稳定的实体和降低的注射活细胞的安全性风险,例如微血管阻塞风险。在本综述中,我们将讨论 MSC-外泌体作为一种创新方法在再生医学中的治疗潜力,并强调 MSC-外泌体在转化医学中的最新知识,重点是体内研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eff0/8274013/e24ccfddd777/12967_2021_2980_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eff0/8274013/52ba4b941bfe/12967_2021_2980_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eff0/8274013/e24ccfddd777/12967_2021_2980_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eff0/8274013/52ba4b941bfe/12967_2021_2980_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eff0/8274013/e24ccfddd777/12967_2021_2980_Fig2_HTML.jpg

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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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本文引用的文献

[1]
Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities.

Stem Cell Res Ther. 2021-5-21

[2]
Metformin facilitates mesenchymal stem cell-derived extracellular nanovesicles release and optimizes therapeutic efficacy in intervertebral disc degeneration.

Biomaterials. 2021-7

[3]
Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders.

Stem Cell Res Ther. 2021-3-18

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Hollow-fiber bioreactor production of extracellular vesicles from human bone marrow mesenchymal stromal cells yields nanovesicles that mirrors the immuno-modulatory antigenic signature of the producer cell.

Stem Cell Res Ther. 2021-2-12

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Mesenchymal stem cell-originated exosomal lncRNA HAND2-AS1 impairs rheumatoid arthritis fibroblast-like synoviocyte activation through miR-143-3p/TNFAIP3/NF-κB pathway.

J Orthop Surg Res. 2021-2-6

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Sci Rep. 2021-1-18

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Intranasal delivery of MSC-derived exosomes attenuates allergic asthma via expanding IL-10 producing lung interstitial macrophages in mice.

Int Immunopharmacol. 2021-2

[8]
Umbilical cord mesenchymal stem cells as well as their released exosomes suppress proliferation of activated PBMCs in multiple sclerosis.

Scand J Immunol. 2021-6

[9]
Bone marrow mesenchymal stem cell-derived exosomes alleviate hyperoxia-induced lung injury via the manipulation of microRNA-425.

Arch Biochem Biophys. 2021-1-15

[10]
Mesenchymal stem cell derived-exosomes: a modern approach in translational medicine.

J Transl Med. 2020-11-27

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