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临床使用脂肪间充质干细胞治疗 COVID-19 患者的原理。

Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients.

机构信息

Personalized Stem Cells, Inc, Poway, CA, USA.

Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA, USA.

出版信息

J Transl Med. 2020 May 18;18(1):203. doi: 10.1186/s12967-020-02380-2.

Abstract

In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, capital city of Hubei province in China. Cases of SARS-CoV-2 infection quickly grew by several thousand per day. Less than 100 days later, the World Health Organization declared that the rapidly spreading viral outbreak had become a global pandemic. Coronavirus disease 2019 (COVID-19) is typically associated with fever and respiratory symptoms. It often progresses to severe respiratory distress and multi-organ failure which carry a high mortality rate. Older patients or those with medical comorbidities are at greater risk for severe disease. Inflammation, pulmonary edema and an over-reactive immune response can lead to hypoxia, respiratory distress and lung damage. Mesenchymal stromal/stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC's impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance. Additionally, MSCs produce molecules that are antimicrobial and reduce pain. Upon administration by the intravenous route, the cells travel directly to the lungs where the majority are sequestered, a great benefit for the treatment of pulmonary disease. The in vivo safety of local and intravenous administration of MSCs has been demonstrated in multiple human clinical trials, including studies of acute respiratory distress syndrome (ARDS). Recently, the application of MSCs in the context of ongoing COVID-19 disease and other viral respiratory illnesses has demonstrated reduced patient mortality and, in some cases, improved long-term pulmonary function. Adipose-derived stem cells (ASC), an abundant type of MSC, are proposed as a therapeutic option for the treatment of COVID-19 in order to reduce morbidity and mortality. Additionally, when proven to be safe and effective, ASC treatments may reduce the demand on critical hospital resources. The ongoing COVID-19 outbreak has resulted in significant healthcare and socioeconomic burdens across the globe. There is a desperate need for safe and effective treatments. Cellular based therapies hold great promise for the treatment of COVID-19. This literature summary reviews the scientific rationale and need for clinical studies of adipose-derived stem cells and other types of mesenchymal stem cells in the treatment of patients who suffer with COVID-19.

摘要

2019 年末,一种新型冠状病毒(SARS-CoV-2)在中国湖北省省会武汉出现。SARS-CoV-2 感染病例每天迅速增加数千例。不到 100 天后,世界卫生组织宣布,这种迅速传播的病毒爆发已成为全球大流行。2019 年冠状病毒病(COVID-19)通常与发热和呼吸道症状有关。它经常发展为严重的呼吸窘迫和多器官衰竭,死亡率很高。老年患者或有合并症的患者患重病的风险更大。炎症、肺水肿和过度活跃的免疫反应可导致缺氧、呼吸窘迫和肺损伤。间充质基质/干细胞(MSCs)具有强大而广泛的免疫调节作用。在动物模型和体外人类肺模型中的多项体内研究表明,MSC 具有令人印象深刻的抑制肺损伤、减少炎症、抑制免疫反应和帮助肺泡液清除的能力。此外,MSCs 产生的分子具有抗菌作用并减轻疼痛。通过静脉途径给药时,细胞直接到达肺部,其中大部分被隔离,这对肺部疾病的治疗非常有益。静脉内和局部给予 MSCs 的体内安全性已在多项人体临床试验中得到证实,包括急性呼吸窘迫综合征(ARDS)的研究。最近,在持续的 COVID-19 疾病和其他病毒性呼吸道疾病的背景下,MSCs 的应用已证明降低了患者死亡率,在某些情况下还改善了长期肺功能。脂肪来源的干细胞(ASC),一种丰富的 MSC 类型,被提议作为 COVID-19 治疗的一种治疗选择,以降低发病率和死亡率。此外,当被证明是安全有效的时,ASC 治疗可能会减少对重症监护资源的需求。持续的 COVID-19 爆发在全球范围内造成了巨大的医疗保健和社会经济负担。迫切需要安全有效的治疗方法。细胞疗法为 COVID-19 的治疗提供了巨大的希望。本文文献综述回顾了脂肪来源干细胞和其他类型间充质干细胞在治疗 COVID-19 患者中的临床研究的科学依据和必要性。

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