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

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Stem Cell Extracellular Vesicles as Anti-SARS-CoV-2 Immunomodulatory Therapeutics: A Systematic Review of Clinical and Preclinical Studies
Stem Cell Reviews and Reports ( IF 4.5 ) Pub Date : 2024-02-23 , DOI: 10.1007/s12015-023-10675-2
Sarah Hamdy Ahmed _{1,

2} , Mohamed Atef AlMoslemany ₁ , Kenneth Whitaker Witwer _{3,

4,

5} , Ahmed Gamal Tehamy ₁ , Nagwa El-Badri ₁

Affiliation

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.

Graphical Abstract

中文翻译：

干细胞胞外囊泡作为抗 SARS-CoV-2 免疫调节疗法：临床和临床前研究的系统评价

背景

COVID-19 迅速升级为全球大流行，即使是无症状患者的传染性也很高。并发症可导致严重肺炎和急性呼吸窘迫综合征（ARDS），这是导致死亡的主要原因。由于其再生和免疫调节能力，干细胞及其衍生的细胞外囊泡 (EV) 被认为是治疗严重肺部疾病（包括与 COVID-19 相关的疾病）的有希望的疗法。在此，我们评估干细胞 EV 在治疗 COVID-19 和并发肺炎、急性肺损伤和 ARDS 方面的安全性和有效性。我们还涵盖相关的临床前研究，以概括基于干细胞 EV 的治疗的当前进展。

方法

使用 PubMed、Cochrane 对照试验中心注册库、Scopus 和 Web of Science，我们检索了所有以英语发表的研究（2000-2023 年），这些研究使用干细胞 EV 治疗 COVID-19、ARDS 或肺炎。所有研究均评估了偏倚风险 (ROB)。

结果

四十八项研究符合我们的纳入标准。据报道，源自不同类型干细胞的各种大小的 EV 是一种潜在的安全有效的疗法，可以减轻由 COVID-19 引起的细胞因子风暴。 EVs 通过减少细胞凋亡、促炎细胞因子、中性粒细胞浸润和 M2 巨噬细胞极化来减轻炎症并再生肺泡上皮。它们还阻止纤维蛋白的产生并促进抗炎细胞因子和内皮细胞连接蛋白的产生。