Lin Feng, Ichim Thomas E, Pingle Sandeep, Jones Lawrence D, Kesari Santosh, Ashili Shashaanka
Research and Development, CureScience, San Diego, CA 92121, United States.
Cancer Center, John Wayne Cancer Institute and Pacific Neuroscience Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, United States.
World J Stem Cells. 2020 Oct 26;12(10):1067-1079. doi: 10.4252/wjsc.v12.i10.1067.
Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a "cytokine storm", as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells (MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing anti-inflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a "living anti-inflammatory", which can "rebalance" the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome.
2019冠状病毒病（COVID-19）是由严重急性呼吸综合征冠状病毒2（SARS-CoV2）引起的一种大流行病，正在全球呈指数级增长。这种疾病的表现具有异质性；然而，重症病例通常会出现各种急性呼吸窘迫综合征样症状、全身炎症反应、凝血病和器官受累。重症COVID-19的一个共同特征是不受控制的免疫激活，传统上称为“细胞因子风暴”，以及免疫调节机制（如调节性T细胞）的缺陷。虽然间充质干细胞（MSCs）本身是细胞因子调节的对象，但它们可以分泌细胞因子来调节免疫细胞，方法是诱导抗炎调节性Treg细胞、巨噬细胞和中性粒细胞；并通过减少T细胞和B细胞、树突状细胞和自然杀伤细胞的激活。因此，它们具有治疗重症COVID-19的潜力。在这里，我们讨论了间充质干细胞作为“活的抗炎剂”的独特能力，它可以“重新平衡”细胞因子/免疫反应以恢复平衡。我们还讨论了当前的间充质干细胞试验，并提出了优化COVID-19急性呼吸窘迫综合征患者间充质干细胞治疗的不同概念。
