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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2020, Vol. 40 Issue (11): 43-55    DOI: 10.13523/j.cb.2005041
综述     
间充质干细胞在2019新型冠状病毒肺炎(COVID-19)中的治疗潜能、临床研究与应用前景*
陈利军1**(),屈晶晶2,项春生1**()
1 浙江大学医学院附属第一医院传染病诊治国家重点实验室 国家感染性疾病临床医学研究中心感染性疾病诊治协同创新中心 杭州 310003
2 浙江大学医学院附属第一医院 杭州 310003
Therapeutic Potentials, Clinical Studies, and Application Prospects of Mesenchymal Stem Cells in 2019 Novel Coronavirus (COVID-19)
CHEN Li-jun1**(),QU Jing-jing2,XIANG Charlie1**()
1 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
2 Department of Respiratory Disease, Thoracic Disease Centre, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
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摘要：

当前因SARS-CoV-2感染而引起的2019新型冠状病毒肺炎(COVID-19)肆虐全球,严重危害人类健康。SARS-CoV-2感染性强,危重症患者死亡率高,尽管各种各样的治疗正在进行临床试验,但目前尚无有效的治疗方法。间充质干细胞(mesenchymal stem cell,MSC)在临床前试验中对多种疾病有良好的治疗效果,因而受到了广泛地关注。MSC可能利用分化潜能诱导分化成功能性肺样细胞、免疫调节与免疫细胞互作、抑制炎症来降低促炎细胞因子分泌、迁移和归巢靶向损伤肺部、抗病毒作用来减少肺上皮细胞中的病毒复制、产生细胞外囊泡来修复受损的组织,进而使COVID-19患者肺功能逐渐恢复正常,缓解并达到治疗COVID-19的目的。综合讨论了COVID-19的基本特征和当前主要治疗手段,同时总结了MSC在COVID-19中的临床研究和当前面临的挑战,探讨了MSC治疗COVID-19的应用前景,为MSC在COVID-19中的治疗提供了理论基础和现实依据。
关键词： 2019新型冠状病毒肺炎;  间充质干细胞;  干细胞治疗;  肺功能修复;  治疗前景    
Abstract:

Currently, the 2019 novel coronavirus (COVID-19) caused by SARS-CoV-2 infection is raging around the world and seriously affects human health. SARS-CoV-2 is highly infectious, and the mortality rate of infected severe patients is high. Although various methods are being tried for clinical trials, no authorised effective treatment is available. Mesenchymal stem cells (MSCs) have attracted wide attention in preclinical trials because they have a good therapeutic effect on a variety of human diseases. MSC may use differentiation potential to induce differentiation into functional pulmonary-like cells, immune regulation interacted with various immune cells, inhibit inflammation to reduce the secretion of pro-inflammatory cytokines, migration and homing to damaged lung, antiviral effects through reduce virus replication in lung epithelial cells, and produces extracellular vesicles to repair damaged tissues, thereby gradually recovering the lung function of COVID-19 patients, alleviating and achieving the goal for treating COVID-19. The basic characteristics of COVID-19 and the current main treatment methods of COVID-19 are comprehensively discussed. At the same time, the clinical research and current challenges are analyzed. In addition, the application prospects of MSC for treating COVID-19 are also discussed. In summary, the research provides a theoretical and practical basis for MSC in the treatment of COVID-19.
Key words: 2019 novel coronavirus (COVID-19)    Mesenchymal stem cells    Stem cell therapy    Pulmonary function repair    Therapeutic prospects
收稿日期: 2020-05-20 出版日期: 2020-12-11
ZTFLH:  Q939.4  
基金资助: * 浙江省重点研发计划应急攻关项目(2020C03125);国家自然科学基金(81900563)
通讯作者: 陈利军,项春生     E-mail: chenlijun@zju.edu.cn;cxiang@zju.edu.cn
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引用本文:

陈利军,屈晶晶,项春生. 间充质干细胞在2019新型冠状病毒肺炎(COVID-19)中的治疗潜能、临床研究与应用前景*[J]. 中国生物工程杂志, 2020, 40(11): 43-55.

CHEN Li-jun,QU Jing-jing,XIANG Charlie. Therapeutic Potentials, Clinical Studies, and Application Prospects of Mesenchymal Stem Cells in 2019 Novel Coronavirus (COVID-19). China Biotechnology, 2020, 40(11): 43-55.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2005041    或    https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I11/43

图1  间充质干细胞治疗2019新型冠状病毒肺炎的潜在机制
注册日期
(2020年)		 注册号 临床试验题目 MSC来源 注册单位
国内
2月4日 ChiCTR2000029569 脐带间充干细胞条件培养基治疗重症及危重症新型冠状病毒肺炎(COVID-19)的安全性和有效性研究:随机对照临床试验 脐带 襄阳市第一人民医院
2月5日 ChiCTR2000029580 芦可替尼联合输注间充质干细胞治疗重症新型冠状病毒肺炎(COVID-19)患者的前瞻性、单盲、随机对照临床研究 不详 华中科技大学同济医学院附属同济医院
2月5日 NCT04252118 Mesenchymal stem cell treatment for pneumonia patients infected with COVID-19 脐带 北京302医院
2月7日 ChiCTR2000029606 宫血干细胞治疗新型冠状病毒肺炎(COVID-19)急性肺损伤(肺炎)的临床研究 宫血 浙江大学医学院附属第一医院
2月13日 NCT04269525 Umbilical cord(UC)-derived mesenchymal stem cells(MSCs) treatment for the 2019-novel coronavirus(nCOV) pneumonia 脐带 武汉大学中南医院
2月14日 ChiCTR2000029816 脐血间充质干细胞用于治疗新型冠状病毒肺炎(COVID-19)的临床研究 脐带血 广州瑞铂茵健康管理咨询有限公司
2月14日 ChiCTR2000029817 脐血NK细胞联合脐血间充质干细胞用于治疗新型冠状病毒肺炎(COVID-19)的临床研究 脐带血 广州瑞铂茵健康管理咨询有限公司
2月18日 ChiCTR2000029990 人间充质干细胞治疗新型冠状病毒感染肺炎(COVID-19)的临床研究 不详 中国医学科学院基础医学研究所
2月18日 NCT04273646 Study of human umbilical cord mesenchymal stem cells in the treatment of severe COVID-19 脐带 华中科技大学同济医学院附属协和医院
2月20日 ChiCTR2000030020 间充质干细胞治疗新型冠状病毒肺炎(COVID-19)的临床应用及其相关基础研究 不详 南华大学附属第二医院
2月22日 ChiCTR2000030088 脐带华通胶源间充质干细胞治疗重症新型冠状病毒肺炎(COVID-19) 脐带华通胶 解放军总医院第六医学中心
2月23日 ChiCTR2000030116 人脐带间充质干细胞治疗重症新型冠状病毒肺炎(COVID-19)致急性呼吸窘迫综合征的安全性和有效性研究 脐带 南昌大学第一附属医院
2月24日 ChiCTR2000030138 人间充质干细胞治疗重症新型冠状病毒(COVID-19)感染肺炎临床研究 脐带 中国人民解放军总医院
2月24日 ChiCTR2000030173 脐带间充质干细胞治疗新型冠状病毒肺炎(COVID-19)关键技术攻关与临床应用示范 脐带 湖南源品细胞生物科技有限公司
2月26日 ChiCTR2000030224 间充质干细胞治疗重症型新型冠状病毒肺炎(COVID-19)的临床研究 不详 华中科技大学同济医学院附属协和医院
2月28日 ChiCTR2000030300 脐带间充质干细胞(hucMSCs)治疗新型冠状病毒肺炎(COVID-19)高危患者 脐带 南京市第二医院
2月28日 NCT04288102 Treatment with human umbilical cord-derived mesenchymal stem cells for severe corona virus disease 2019 (COVID-19) 脐带 北京302医院
3月3日 ChiCTR2000030484 脐带间充质干细胞联合细胞外泌体静脉输注对新型冠状病毒肺炎(COVID-19)肺损伤修复的临床应用研究 脐带 湖北十堰市太和医院
3月15日 ChiCTR2000030835 间充质干细胞(MSC)治疗重型新型冠状病毒肺炎(COVID-19)的有效性临床研究 脐带 新乡医学院第一附属医院
注册日期
(2020年)		 注册号 临床试验题目 MSC来源 注册单位
3月15日 NCT04346368 Bone marrow-derived mesenchymal stem cell treatment for severe patients with coronavirus disease 2019 (COVID-19) 骨髓 广州呼吸疾病研究所
3月16日 ChiCTR2000030866 脐带间充质干细胞治疗重型和危重型新型冠状病毒肺炎(COVID-19)的开放性临床观察研究 脐带 长沙市第一医院
3月18日 ChiCTR2000030944 人自然杀伤细胞联合间充质干细胞治疗重症新型冠状病毒肺炎(COVID-19)的临床研究 脐带血 南昌大学第二附属医院
3月27日 ChiCTR2000031319 异体人牙髓间充质干细胞治疗新型冠状病毒肺炎(COVID-19)重症肺炎的安全性和有效性研究 牙髓 武汉大学人民医院
3月31日 ChiCTR2000031430 人间充质干细胞治疗新型冠状病毒肺炎(COVID-19)患者肺间质性损害的临床研究 不详 中国人民解放军总医院第五医学中心
4月2日 ChiCTR2000031494 间充质干细胞治疗重症新冠肺炎(COVID-19)的临床研究 脐带 黄石市中医医院(市传染病医院)
4月7日 NCT04336254 Safety and efficacy study of allogeneic human dental pulp mesenchymal stem cells to treat severe COVID-19 patients 牙髓 武汉大学人民医院
4月9日 NCT04339660 Clinical research of human mesenchymal stem cells in the treatment of COVID-19 pneumonia 脐带 武汉科技大学附属普仁医院
5月1日 NCT04371601 Safety and effectiveness of mesenchymal stem cells in the treatment of pneumonia of coronavirus disease 2019 不详 南京军区福州总医院
国外
2月3日 NCT03042143 Repair of acute respiratory distress syndrome by stromal cell administration (REALIST) (COVID-19) (REALIST) 脐带 Belfast Health and Social Care Trust, United Kingdom
3月18日 NCT04313322 Treatment of COVID-19 patients using Wharton’s Jelly-Mesenchymal stem cells 脐带华通胶 Stem Cells ArabiaAmman, Jordan
4月3日 NCT04333368 Cell therapy using umbilical cord-derived mesenchymal stromal cells in SARS-CoV-2-related ARDS (STROMA-CoV2) 脐带 Assistance Publique-H?pitaux de Paris, France
4月14日 NCT04345601 Mesenchymal stromal cells for the treatment of SARS-CoV-2 induced acute respiratory failure (COVID-19 Disease) 骨髓 LaQuisa Hill, Baylor College of Medicine, USA
4月16日 NCT04349631 A clinical trial to determine the safety and efficacy of hope biosciences autologous mesenchymal stem cell therapy (HB-adMSCs) to provide protection against COVID-19 脂肪 Hope Biosciences, USA
4月20日 NCT04352803 Adipose mesenchymal cells for abatement of SARS-CoV-2 respiratory compromise in COVID-19 disease 脂肪 Regeneris Medical, USA
4月21日 NCT04355728 Use of UC-MSCs for COVID-19 patients 脐带 Camillo Ricordi, University of Miami, USA
4月24日 NCT04361942 Treatment of severe COVID-19 pneumonia with allogeneic mesenchymal stromal cells (COVID_MSV) 不详 Hospital Universitario Rio Hortega
Valladolid, Spain
4月28日 NCT04366063 Mesenchymal stem cell therapy for SARS-CoV-2-related acute respiratory distress syndrome 不详 Royan Institute, Iran
5月1日 NCT04371393 MSCs in COVID-19 ARDS 不详 Annetine Gelijns, Icahn School of Medicine at Mount Sinai,USA
注册日期
(2020年)		 注册号 临床试验题目 MSC来源 注册单位
5月6日 NCT04377334 Mesenchymal stem cells (MSCs) in inflammation-resolution programs of coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS) 骨髓 University Hospital Tuebingen
Tuebingen, Germany
5月11日 NCT04382547 Treatment of covid-19 associated pneumonia with allogenic pooled olfactory mucosa-derived mesenchymal stem cells 黏膜 Institute of Biophysics and Cell Engineering of National Academy of Sciences of Belarus, Belarus
5月15日 NCT04390139 Efficacy and safety evaluation of mesenchymal stem cells for the treatment of patients with respiratory distress due to COVID-19 (COVIDMES) 脐带华通胶 Banc de Sang i Teixits, Spain
5月15日 NCT04390152 Safety and efficacy of intravenous Wharton’s Jelly derived mesenchymal stem cells in acute respiratory distress syndrome due to COVID 19 脐带华通胶 BioXcellerator, USA
5月19日 NCT04392778 Clinical use of stem cells for the treatment of COVID-19 不详 SBü Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Turkey
5月21日 NCT04397796 Study of the safety of therapeutic Tx with immunomodulatory MSC in adults With COVID-19 infection requiring mechanical ventilation 骨髓 NantKwest, Inc., USA
5月22日 NCT04399889 hCT-MSCs for COVID19 ARDS 脐带 Joanne Kurtzberg, MD, Duke University, USA
5月22日 NCT04400032 Cellular immuno-therapy for COVID-19 acute respiratory distress syndrome - vanguard (CIRCA-19) 骨髓 Ottawa Hospital Research Institute, Canada
6月4日 NCT04416139 Mesenchymal stem cell for acute respiratory distress syndrome due for COVID-19 (COVID-19) 脐带 Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico
6月11日 NCT04428801 Autologous adipose-derived stem cells (AdMSCs) for COVID-19 脂肪 Celltex Therapeutics Corporation, USA
6月12日 NCT04429763 Safety and efficacy of mesenchymal stem cells in the management of severe COVID-19 pneumonia (CELMA) 脐带 Trustem, USA
6月18日 NCT04437823 Efficacy of intravenous infusions of stem cells in the treatment of COVID-19 patients 脐带 Jinnah Hospital, Pakistan
6月23日 NCT04444271 Mesenchymal stem cell infusion for COVID-19 infection 骨髓 National Institute of Blood and Marrow Transplant (NIBMT), Pakistan
6月24日 NCT04445454 Mesenchymal stromal cell therapy for severe COVID-19 infection 骨髓 Yves Beguin, University of Liege, Belgium
6月25日 NCT04447833 Mesenchymal stromal cell therapy for the treatment of acute respiratory distress syndrome (ARDS-MSC-205) 骨髓 Uppsala University, Sweden
6月30日 NCT04452097 Use of hUC-MSC product (BX-U001) for the treatment of COVID-19 with ARDS 脐带 Baylx Inc., USA
7月2日 NCT04456361 Use of mesenchymal stem cells in acute respiratory distress syndrome caused by COVID-19 脐带华通胶 Instituto de Medicina Regenerativa
Tijuana, Baja California, Mexico
7月7日 NCT04457609 Administration of allogenic uc-mscs as adjuvant therapy for critically-Ill COVID-19 patients 脐带 Ismail Hadisoebroto Dilogo, Indonesia University, Indonesia
注册日期
(2020年)		 注册号 临床试验题目 MSC来源 注册单位
7月10日 NCT04467047 Safety and feasibility of allogenic MSC in the treatment of COVID-19 (COVID19) 不详 Hospital de Clinicas de Porto Alegre, Brazil
7月10日 NCT04466098 Multiple dosing of mesenchymal stromal cells in patients with ARDS (COVID-19) 不详 Masonic Cancer Center, University of Minnesota, USA
7月29日 NCT04490486 Umbilical cord tissue (UC) derived mesenchymal stem cells (MSCs) versus placebo to treat acute pulmonary inflammation due to COVID-19 (COVID-19) 脐带 Joshua M Hare, University of Miami, USA
7月31日 NCT04494386 Umbilical cord lining stem cells (ULSC) in patients with COVID-19 ARDS (ULSC) 脐带 Restem, LLC., USA
8月21日 NCT04522986 An exploratory study of ADR-001 in patients with severe pneumonia caused by SARS-CoV-2 infection (COVID-19) 脂肪 Rohto Pharmaceutical Co., Ltd., Japan
8月25日 NCT04525378 MSC-based therapy in COVID-19-associated acute respiratory distress syndrome 不详 D’Or Institute for Research and Education, Brazil
9月2日 NCT04535856 Therapeutic study to evaluate the safety and efficacy of DW-MSC in COVID-19 patients (DW-MSC) 不详 Ina-Respond, Indonesia
9月3日 NCT04537351 The mesenchymal COVID-19 trial: a pilot study to investigate early efficacy of MSCs in adults with COVID-19 (MEND) Cymerus Cynata Therapeutics Limited, Australia
9月25日 NCT04565665 Cord blood-derived mesenchymal stem cells for the treatment of COVID-19 related acute respiratory distress syndrome 脐带血 M.D. Anderson Cancer Center, USA
表1  国内外注册的MSC治疗COVID-19临床试验
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