Tri State Spine Care Institute.
Wright State University School of Medicine, Dayton, OH.
Pain Physician. 2020 Aug;23(4S):S391-S420.
Although only a small percentage of patients with COVID-19 deteriorate to a critical condition, because of the associated high mortality rate and the sheer number of cases, it imposes a tremendous burden on the society and unprecedented strains the health care resources. Albeit lung is the primary organ involved resulting in acute respiratory distress syndrome (ARDS), many patients additionally present with secondary multiorgan failure. Unfortunately, there is no definitive or curative treatment for this condition, and the management has been predominantly confined to supportive care, which necessitates an urgent need for novel therapies. Mesenchymal stem cell (MSC) therapy has a vast array of preclinical data and early, preliminary clinical data that suggests its potential to regenerate and restore the function of damaged tissues and organs. To date, there has been no review of all the clinical trials that have assessed the safety and efficacy of MSC therapy in organ failure commonly seen in seriously complicated COVID-19 patients.
To evaluate the effectiveness of MSC therapy in managing multiorgan failure, utilizing currently available literature.
A review of human randomized controlled trials (RCTs) and observational studies assessing the role of MSC therapy in managing multiorgan failure.
PubMed, Cochrane Library, US National Guideline Clearinghouse, Google Scholar, and prior systematic reviews and reference lists were utilized in the literature search from 1990 through May 2020. Studies that included embryonic stem cells, induced pluripotent stem cells, differentiated MSCs into specific lineage cells, and hematopoietic stem cells were excluded. Trials with intraorgan infiltration of MSC were also excluded.
The primary outcome evaluated the improvement in clinical assessment scores and indices of organ function. The secondary outcome assessed the safety of MSC therapy in the clinical trials.
Based on search criteria, 12 studies were found for lung, 52 for heart, 23 for liver, 16 for stroke, and 9 for kidney. Among the 6 studies that specifically assessed the effectiveness of MSC therapy in ARDS, 4 showed positive outcomes. Forty-one of the 52 trials that examined ischemic and nonischemic heart failure reported beneficial effects. Twenty of 23 trials for liver failure from different etiologies revealed favorable outcomes. Nine out of the 15 studies evaluating stroke had satisfactory effects. However, only 3 out of the 9 studies for kidney failure showed positive results. Nonexpanded bone marrow mononuclear cells were used in most of the negative studies. The incidence of disease worsening or major complications was extremely rare from MSC therapy.
Among the studies evaluated, although there were many RCTs, there were also numerous case series. Additionally, most recruited a small number of patients.
MSC therapy seems to be promising to treat multiorgan failure from COVID-19. More studies are urgently needed to assess both safety and efficacy.
尽管只有一小部分 COVID-19 患者病情恶化至危急状态，但由于其相关的高死亡率和庞大的病例数量，这给社会带来了巨大的负担，并对医疗资源造成了前所未有的压力。尽管肺是导致急性呼吸窘迫综合征（ARDS）的主要器官，但许多患者还会出现继发性多器官衰竭。不幸的是，目前尚无针对这种疾病的明确或治愈性治疗方法，其治疗主要局限于支持性护理，这迫切需要新型疗法。间充质干细胞（MSC）疗法具有广泛的临床前数据和早期初步临床数据，表明其具有再生和恢复受损组织和器官功能的潜力。迄今为止，尚无针对评估 MSC 疗法在严重 COVID-19 患者常见的器官衰竭中的安全性和疗效的所有临床试验进行综述。
评估 MSC 疗法在治疗多器官衰竭中的有效性，利用现有文献。
对评估 MSC 疗法在治疗多器官衰竭中的作用的人类随机对照试验（RCT）和观察性研究进行综述。
从 1990 年至 2020 年 5 月，我们在文献检索中使用了 PubMed、Cochrane 图书馆、美国国家指南交换中心、Google Scholar 以及先前的系统评价和参考文献列表。排除了胚胎干细胞、诱导多能干细胞、将 MSC 分化为特定谱系细胞以及造血干细胞的研究。也排除了 MSC 向器官内浸润的试验。
主要结局是评估临床评估评分和器官功能指标的改善。次要结局是评估临床试验中 MSC 治疗的安全性。
根据搜索标准，发现了 12 项关于肺的研究、52 项关于心脏的研究、23 项关于肝脏的研究、16 项关于中风的研究和 9 项关于肾脏的研究。在专门评估 MSC 疗法在 ARDS 中有效性的 6 项研究中，有 4 项显示出积极的结果。52 项关于缺血性和非缺血性心力衰竭的研究中有 41 项报告了有益的效果。23 项不同病因的肝衰竭试验中有 20 项显示出有利的结果。9 项评估中风的研究中有 8 项效果令人满意。然而，仅有 9 项肾脏衰竭研究中的 3 项显示出阳性结果。大多数阴性研究使用了未经扩增的骨髓单核细胞。从 MSC 治疗中观察到疾病恶化或主要并发症的发生率极低。
在评估的研究中，虽然有许多 RCT，但也有许多病例系列研究。此外，大多数研究招募的患者数量较少。
MSC 疗法似乎有望治疗 COVID-19 引起的多器官衰竭。迫切需要更多的研究来评估安全性和疗效。
