W. M. Keck Center for Collaborative Neuroscience, Rutgers Stem Cell Research Center, Department of Cell Biology & Neuroscience, Rutgers University, Piscataway, NJ, USA.
Department of Medicine, North Shore University Hospital, Manhasset, NY, USA.
Stem Cells Transl Med. 2022 Nov 18;11(11):1103-1112. doi: 10.1093/stcltm/szac067.
Patients with severe COVID-19 experience cytokine storm, an uncontrolled upregulation of pro-inflammatory cytokines, which if unresolved leads to acute respiratory distress syndrome (ARDS), organ damage, and death. Treatments with mesenchymal stromal cells (MSC) [Viswanathan S, Shi Y, Galipeau J, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy. 2019;21:1019-1024] appear to be effective in reducing morbidity and mortality. MSC respond to pro-inflammatory cytokines by releasing anti-inflammatory factors and mobilizing immune cells. We analyzed 82 COVID-19 clinical trials registered at ClinicalTrials.gov to determine MSC dosing, routes of administration, and outcome measures. Nearly all trials described the use of intravenous delivery with most doses ranging between 50 and 125 million MSC/treatment, which overlaps with a minimal effective dose range that we described previously. We also searched the literature to analyze clinical trial reports that used MSC to treat COVID-19. MSC were found to improve survival and oxygenation, increase discharge from intensive care units and hospitals, and reduce levels of pro-inflammatory markers. We report on a 91-year-old man with severe COVID-19 who responded rapidly to MSC treatment with transient reductions in several pro-inflammatory markers and delayed improvement in oxygenation. The results suggest that frequent monitoring of pro-inflammatory markers for severe COVID-19 will provide improved treatment guidelines by determining relationships between cytokine storms and ARDS. We propose that markers for cytokine storm are leading indicators for ARDS and that measurement of cytokines will indicate earlier treatment with MSC than is performed now for ARDS in severe COVID-19.
患有严重 COVID-19 的患者会经历细胞因子风暴，即促炎细胞因子的失控上调，如果得不到解决，会导致急性呼吸窘迫综合征（ARDS）、器官损伤和死亡。间充质基质细胞（MSC）[Viswanathan S、Shi Y、Galipeau J 等人。间充质干细胞与基质细胞：国际细胞与基因治疗协会间充质干细胞委员会关于命名的立场声明。细胞治疗。2019;21:1019-1024]的治疗方法似乎可以有效降低发病率和死亡率。MSC 通过释放抗炎因子和动员免疫细胞来应对促炎细胞因子。我们分析了在 ClinicalTrials.gov 上注册的 82 项 COVID-19 临床试验，以确定 MSC 的剂量、给药途径和结果测量。几乎所有的试验都描述了静脉给药的使用，大多数剂量范围在 5000 万到 1.25 亿 MSC/治疗之间，这与我们之前描述的最小有效剂量范围重叠。我们还搜索了文献，分析了使用 MSC 治疗 COVID-19 的临床试验报告。发现 MSC 可以提高生存率和氧合，增加从重症监护病房和医院出院的人数，并降低促炎标志物的水平。我们报告了一名 91 岁的严重 COVID-19 男性患者，他对 MSC 治疗反应迅速，几种促炎标志物短暂下降，氧合改善延迟。结果表明，对严重 COVID-19 的促炎标志物进行频繁监测将通过确定细胞因子风暴与 ARDS 之间的关系，提供更好的治疗指南。我们提出，细胞因子风暴的标志物是 ARDS 的早期指标，测量细胞因子将比现在对严重 COVID-19 中的 ARDS 更早地指示用 MSC 进行治疗。
