Stem Cell Extracellular Vesicles as Anti-SARS-CoV-2 Immunomodulatory Therapeutics: A Systematic Review of Clinical and Preclinical Studies.

IF 4.5 3区医学 Q2 CELL & TISSUE ENGINEERING Stem Cell Reviews and Reports Pub Date : 2024-05-01 Epub Date: 2024-02-23 DOI:10.1007/s12015-023-10675-2

Sarah Hamdy Ahmed, Mohamed Atef AlMoslemany, Kenneth Whitaker Witwer, Ahmed Gamal Tehamy, Nagwa El-Badri

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Abstract

Background: COVID-19 rapidly escalated into a worldwide pandemic with elevated infectivity even from asymptomatic patients. Complications can lead to severe pneumonia and acute respiratory distress syndrome (ARDS), which are the main contributors to death. Because of their regenerative and immunomodulatory capacities, stem cells and their derived extracellular vesicles (EVs) are perceived as promising therapies against severe pulmonary conditions, including those associated with COVID-19. Herein, we evaluate the safety and efficacy of stem cell EVs in treating COVID-19 and complicating pneumonia, acute lung injury, and ARDS. We also cover relevant preclinical studies to recapitulate the current progress in stem cell EV-based therapy.

Methods: Using PubMed, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science, we searched for all English-language published studies (2000-2023) that used stem cell EVs as a therapy for COVID-19, ARDS, or pneumonia. The risk of bias (ROB) was assessed for all studies.

Results: Forty-eight studies met our inclusion criteria. Various-sized EVs derived from different types of stem cells were reported as a potentially safe and effective therapy to attenuate the cytokine storm induced by COVID-19. EVs alleviated inflammation and regenerated the alveolar epithelium by decreasing apoptosis, proinflammatory cytokines, neutrophil infiltration, and M2 macrophage polarization. They also prevented fibrin production and promoted the production of anti-inflammatory cytokines and endothelial cell junction proteins.

Conclusion: Similar to their parental cells, stem cell EVs mediate lung tissue regeneration by targeting multiple pathways and thus hold promise in promoting the recovery of COVID-19 patients and improving the survival rate of severely affected patients.

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干细胞胞外囊泡作为抗 SARS-CoV-2 免疫调节治疗药物：临床和临床前研究的系统回顾。

背景：COVID-19 迅速升级为全球大流行病，即使无症状患者也具有很高的传染性。并发症可导致重症肺炎和急性呼吸窘迫综合征（ARDS），是造成死亡的主要原因。干细胞及其衍生的细胞外囊泡（EVs）具有再生和免疫调节能力，因此被认为是治疗严重肺部疾病（包括与COVID-19相关的疾病）的有前途的疗法。在此，我们评估了干细胞EVs治疗COVID-19及并发肺炎、急性肺损伤和ARDS的安全性和有效性。我们还涵盖了相关的临床前研究，以回顾干细胞EV疗法目前的进展：方法：我们利用PubMed、Cochrane Central Register of Controlled Trials、Scopus和Web of Science检索了所有使用干细胞EV治疗COVID-19、ARDS或肺炎的英文发表研究（2000-2023年）。对所有研究进行了偏倚风险（ROB）评估：结果：48项研究符合我们的纳入标准。据报道，从不同类型干细胞中提取的不同大小的EVs可能是一种安全有效的疗法，可减轻COVID-19诱导的细胞因子风暴。EVs通过减少细胞凋亡、促炎细胞因子、中性粒细胞浸润和M2巨噬细胞极化，缓解了炎症并使肺泡上皮再生。它们还阻止了纤维蛋白的生成，促进了抗炎细胞因子和内皮细胞连接蛋白的生成：结论：与亲代细胞类似，干细胞EVs通过靶向多种途径介导肺组织再生，因此有望促进COVID-19患者的康复，并提高严重患者的存活率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Stem Cell Reviews and Reports 医学-细胞生物学

CiteScore

9.30

自引率

4.20%

发文量

审稿时长

3 months

期刊介绍： The purpose of Stem Cell Reviews and Reports is to cover contemporary and emerging areas in stem cell research and regenerative medicine. The journal will consider for publication: i) solicited or unsolicited reviews of topical areas of stem cell biology that highlight, critique and synthesize recent important findings in the field. ii) full length and short reports presenting original experimental work. iii) translational stem cell studies describing results of clinical trials using stem cells as therapeutics. iv) papers focused on diseases of stem cells. v) hypothesis and commentary articles as opinion-based pieces in which authors can propose a new theory, interpretation of a controversial area in stem cell biology, or a stem cell biology question or paradigm. These articles contain more speculation than reviews, but they should be based on solid rationale. vi) protocols as peer-reviewed procedures that provide step-by-step descriptions, outlined in sufficient detail, so that both experts and novices can apply them to their own research. vii) letters to the editor and correspondence. In order to facilitate this exchange of scientific information and exciting novel ideas, the journal has created five thematic sections, focusing on: i) the role of adult stem cells in tissue regeneration; ii) progress in research on induced pluripotent stem cells, embryonic stem cells and mechanism governing embryogenesis and tissue development; iii) the role of microenvironment and extracellular microvesicles in directing the fate of stem cells; iv) mechanisms of stem cell trafficking, stem cell mobilization and homing with special emphasis on hematopoiesis; v) the role of stem cells in aging processes and cancerogenesis.