Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia
Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia
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ACE2(-) 间充质干细胞移植可改善 COVID-19 肺炎患者的预后
DOI：
10.14336/ad.2020.0228
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发表时间：
2020-04-01
影响因子：
7.4
通讯作者：
Zhao, Robert Chunhua
中科院分区：
文献类型：
--
作者：
Leng, Zikuan;Zhu, Rongjia;Zhao, Robert Chunhua
一种冠状病毒（HCoV-19）导致了中国武汉的新型冠状病毒病（COVID-19）爆发。预防和逆转细胞因子风暴可能是拯救重症COVID-19肺炎患者的关键。骨髓间充质干细胞（Mesenchymal stem cells，MSCs）具有广泛的免疫调节功能。本研究旨在调查MSC移植是否改善了2020年1月23日至2020年2月16日在中国北京佑安医院入选的7名COVID-19肺炎患者的结局。观察7例患者注射MSC后14 d的临床疗效、炎症和免疫功能变化及不良反应。骨髓间充质干细胞可以治愈或显着改善7例患者的功能结果，没有观察到不良反应。这7例患者的肺功能和症状在MSC移植后2天明显改善。其中，2名普通型和1名重症患者在治疗后10天内康复出院。治疗后3-6 d外周血淋巴细胞增多，C反应蛋白下降，过度活化的分泌精氨酸的免疫细胞CXCR 3 + CD 4 + T细胞、CXCR 3 + CD 8 + T细胞和CXCR 3 + NK细胞消失。另外，一组CD 14 + CD 11 c + CD 11b（mid）调节性DC细胞群明显增加。同时，与安慰剂对照组相比，MSC治疗组的TNF-α水平显著降低，而IL-10水平升高。此外，基因表达谱显示MSC是ACE 2-和TMPRSS 2-，这表明MSC没有COVID-19感染。因此，静脉移植MSCs治疗COVID-19肺炎患者是安全有效的，特别是对于重症患者。
A coronavirus (HCoV-19) has caused the novel coronavirus disease (COVID-19) outbreak in Wuhan, China. Preventing and reversing the cytokine storm may be the key to save the patients with severe COVID-19 pneumonia. Mesenchymal stem cells (MSCs) have been shown to possess a comprehensive powerful immunomodulatory function. This study aims to investigate whether MSC transplantation improves the outcome of 7 enrolled patients with COVID-19 pneumonia in Beijing YouAn Hospital, China, from Jan 23, 2020 to Feb 16, 2020. The clinical outcomes, as well as changes of inflammatory and immune function levels and adverse effects of 7 enrolled patients were assessed for 14 days after MSC injection. MSCs could cure or significantly improve the functional outcomes of seven patients without observed adverse effects. The pulmonary function and symptoms of these seven patients were significantly improved in 2 days after MSC transplantation. Among them, two common and one severe patient were recovered and discharged in 10 days after treatment. After treatment, the peripheral lymphocytes were increased, the C-reactive protein decreased, and the overactivated cytokine-secreting immune cells CXCR3+CD4+ T cells, CXCR3+CD8+ T cells, and CXCR3+ NK cells disappeared in 3-6 days. In addition, a group of CD14+CD11c+CD11b(mid) regulatory DC cell population dramatically increased. Meanwhile, the level of TNF-alpha was significantly decreased, while IL-10 increased in MSC treatment group compared to the placebo control group. Furthermore, the gene expression profile showed MSCs were ACE2 - and TMPRSS2 - which indicated MSCs are free from COVID-19 infection. Thus, the intravenous transplantation of MSCs was safe and effective for treatment in patients with COVID-19 pneumonia, especially for the patients in critically severe condition.