Mesenchymal stromal cell therapy for COVID-19-induced ARDS patients: a successful phase 1, control-placebo group, clinical trial.
Mesenchymal stromal cell therapy for COVID-19-induced ARDS patients: a successful phase 1, control-placebo group, clinical trial.
复制标题
DOI：
10.1186/s13287-022-02920-1
复制
发表时间：
2022-06-28
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
作者：
急性呼吸窘迫综合征（ARDS）是新型COVID-19大流行的破坏性并发症，与大量炎症细胞因子的释放直接相关。由于其免疫调节特性，间充质间质细胞（MSCs）为治疗这种疾病提供了一种有希望的方法。为此，本研究设计为一项单中心、开放标签、1期临床试验，以对照组为基础，检验三次注射脐带源性间充质干细胞（UC-MSCs）对轻中度covid -19诱导的ARDS患者的安全性，并探讨其可能的效力。20例确诊的COVID-19轻中度ARDS患者进入研究，分为两组：对照组（标准治疗）和干预组（标准治疗+ UC-MSCs）。患者每隔一天静脉输注3次UC-MSCs（每次1 ×细胞/kg BW）。在17天的随访期间，评估呼吸标志物、CRP水平和特异性血清细胞因子4次（第0、5、10和17天）。在研究过程中，细胞移植后未出现严重不良反应。此外，SPO2/FIO2比值及血清CRP水平均有显著改善。另一方面，血清细胞因子IL-6、IFN-g、TNF-α、IL-17 a水平显著降低（P < 0.05），血清细胞因子TGF-B、IL-1B、IL-10水平显著升高。此外，在研究期间，患者的CT扫描图像未见明显变化。我们获得的结果表明，在非严重的covid -19诱导的ARDS患者中多次静脉移植同种异体UC-MSCs是一种安全的手术。此外，这种干预是减少细胞因子风暴和恢复呼吸功能的有希望的途径。事实上，需要更多的临床试验和更大的样本量来证实这些结果。该临床试验已在伊朗临床试验注册中心注册（ID: IRCT20160809029275N1, 2020.05.30）。
Acute respiratory distress syndrome (ARDS) is the devastating complication of the new COVID-19 pandemic, directly correlated with releasing large amounts of inflammatory cytokines. Due to their immunoregulatory features, mesenchymal stromal cells (MSCs) provide a promising approach against this disease. In this regard, this study was designed as a single-center, open-label, phase 1 clinical trial with a control group to examine the safety and explore the possible potency of three injections of umbilical cord-derived MSCs (UC-MSCs) in mild–moderate COVID-19-induced ARDS patients. Twenty confirmed COVID-19 patients with mild-to-moderate ARDS degree entered the study and were divided into two groups: control group (standard care) and intervention group (standard care + UC-MSCs). The patients received three intravenous infusions of UC-MSCs (1 × cells/kg BW per injection) every other day. Respiratory markers, CRP levels and specific serum cytokines were assessed four times (days of 0, 5, 10 and 17) during the 17-day follow-up period. During the study, there were no serious adverse effects after cell transplantations. Besides, significant improvement in SPO2/FIO2 ratio and serum CRP levels was observed. On the other hand, a significant decrease (P < 0.05) in serum cytokine levels of IL-6, IFN-g, TNF-α, IL-17 A and a significant increase in serum cytokine levels of TGF-B, IL-1B and IL-10 were observed. Also, no significant changes were observed in CT scan images of patients during the study period. Our obtained results demonstrated that multiple intravenous transplantations of allogenic UC-MSCs in non-severe COVID-19-induced ARDS patients are a safe procedure. In addition, this intervention is a hopeful approach to decline cytokine storm and recover respiratory functions. Indeed, more clinical trials with larger sample sizes are required to confirm these results. Trial registration This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N1 at 2020.05.30).