Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19:a phase 1 clinical trial

作     者：Fanping Meng Ruonan Xu Siyu Wang Zhe Xu Chao Zhang Yuanyuan Li Tao Yang Lei Shi Junliang Fu Tianjun Jiang Lei Huang Peng Zhao Xin Yuan Xing Fan Ji-Yuan Zhang Jinwen Song Dawei Zhang Yanmei Jiao Limin Liu Chunbao Zhou Markus Maeurer Alimuddin Zumla Ming Shi Fu-Sheng Wang Fanping Meng;Ruonan Xu;Siyu Wang;Zhe Xu;Chao Zhang;Yuanyuan Li;Tao Yang;Lei Shi;Junliang Fu;Tianjun Jiang;Lei Huang;Peng Zhao;Xin Yuan;Xing Fan;Ji-Yuan Zhang;Jinwen Song;Dawei Zhang;Yanmei Jiao;Limin Liu;Chunbao Zhou;Markus Maeurer;Alimuddin Zumla;Ming Shi;Fu-Sheng Wang

作者机构：Department of Infectious DiseasesFifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijingChina Immunotherapy ProgrammeChampalimaud Centre for the UnknownLisbonPortugal I Med ClinicUniversity of MainzMainzGermany Department of InfectionDivision of Infection and ImmunityUniversity College LondonLondonUK National Institute for Health Research Biomedical Research CentreUniversity College London Hospitals NHS Foundation TrustLondonUK 

出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)

年 卷 期：2020年第5卷第1期

页      面：1010-1016页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by The National Key R&D Program of China(2020YFC0841900,2020YFC0844000) The Innovation Groups of the National Natural Science Foundation of China(81721002) The National Science and Technology Major Project(2017YFA0105703) The Military Emergency Research Project for COVID-19(BWS20J006) The Project for Innovation of Military Medicine of China(16CXZ045). 

主　　题：patients infusion clinical 

摘      要：No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical evaluation.We performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease.The study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and 6.Both groups received standard COVID-treatment regimens.Adverse events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed.No serious UC-MSCs infusion-associated adverse events were observed.Two patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion.Mechanical ventilation was required in one patient in the treatment group compared with four in the control group.All patients recovered and were discharged.Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated.Phase 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.