Research Progress in the Treatment of COVID-19 with Mesenchymal Stem Cells

doi:10.19803/j.1672-8629.2021.10.05

Abstract

Abstract: COVID-19 caused by SARS-CoV-2 is characterized by respiratory tract infections that range from mild upper respiratory tract infection to severe pneumonia, acute respiratory distress syndrome and even death. Antiviral drugs with specific therapeutic effect against COVID-19 are currently lacking, and there is an urgent need for clinical treatment of infected individuals (especially severe and critical patients). In recent years, mesenchymal stem cells (MSC) have attracted much attention in clinical trials because of their immunomodulatory and regeneration characteristics. This article reviews the immunomodulatory effect of MSC on COVID-19 and the current clinical trials so as to contribute to research on MSC.

Key words: SARS-CoV-2, COVID-19, mesenchymal stem cells

CLC Number:

R978.7

SONG Meihua, GE Ziruo, CHEN Zhihai, XU Yanli. Research Progress in the Treatment of COVID-19 with Mesenchymal Stem Cells[J]. Chinese Journal of Pharmacovigilance, 2021, 18(10): 920-923.

References

[1] Worldometers.COVID-19 coronavirus pandemic.[EB/OL].(2021-06-01)[2021-06-01]. https://www.worldometers.info/coronavirus/.
[2] Ji Y, Ma Z, Peppelenbosch MP, et al.Potential association between COVID-19 mortality and health-care resource availability[J]. Lancet Glob Health, 2020: 8(4): e480.
[3] Baud D, Qi X, Nielsen-Saines K, et al.Real estimates of mortality following COVID-19 infection[J]. Lancet Infect Dis, 2020, 20(7): 773.
[4] Zhu N, Zhang D, Wang W, et al.A novel coronavirus from patients with pneumonia in China, 2019[J]. N Engl J Med, 2020, 382(8): 727-733.
[5] Millet JK, Whittaker GR.Host cell entry of middle east respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein[J]. Proc Natl Acad Sci USA, 2014, 111(42): 15214-15219.
[6] Belouzard S, Chu VC, Whittaker GR.Activation of the SARS corona-virus spike protein via sequential proteolytic cleavage at two distinct sites[J]. Proc Natl Acad Sci USA, 2009, 6(14): 5871-5876.
[7] Walls AC, Tortorici MA, Snijder J, et al.Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion[J]. Proc Natl Acad Sci USA, 2017, 114(42): 11157-11162.
[8] Wrapp D, Wang N, Corbett KS, et al.Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation[J]. Science, 2020, 367(6483): 1260-1263.
[9] Walls AC, Park YJ, Tortorici MA, et al.Structure, function, and Antigenicity of the SARS-CoV-2 spike glycoprotein[J]. Cell, 2020, 181(2): 281-292.
[10] Letko M, Marzi A, Munster V.Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses[J]. Nat Microbiol, 2020, 5(4): 562-569.
[11] Yan R, Zhang Y, Li Y, et al.Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2[J]. Science, 2020, 367(6485): 1444-1448.
[12] Heurich A, Hofmann-Winkler H, Gierer S, et al.TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein[J]. J Virol, 2014, 88(2): 1293-1307.
[13] Bertram S, Heurich A, Lavender H, et al.Influenza and SARS-coronavirus activating proteases TMPRSS2 and HAT are expressed at multiple sites in human respiratory and gastrointestinal tracts[J]. PLoS One, 2012, 7(4): e35876.
[14] Liu J, Li S, Liu J, et al.Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients[J]. EBio Medicine, 2020, 55: 102763.
[15] Huang C, Wang Y, Li X, et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China[J]. Lancet, 2020, 395(10223): 497-506.
[16] Ruan Q, Yang K, Wang W, et al.Correction to: clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China[J]. Intensive Care Med, 2020, 46(6): 1294-1297.
[17] Anasiz Y, Ozgul RK, Uckan-Cetinkaya D.A new chapter for mesenchymal stem cells: decellularized extracellular matrices[J]. Stem Cell Rev Rep, 2017, 13(5): 587-597.
[18] Alstrup T, Eijken M, Bohn AB, et al.Isolation of adipose tissue -derived stem cells:enzymatic digestion in combination with mechanical distortion to increase adipose tissue-derived stem cell yield from human aspirated fat[J]. Curr Protoc Stem Cell Biol, 2019, 48(1): e68.
[19] Bieback K, Netsch P.Isolation, culture, and characterization of human umbilical cord blood-derived mesenchymal stromal cells[J]. Methods Mol Biol, 2016, 1416: 245-258.
[20] Li J, Xu SQ, Zhao YM, et al.Comparison of the biological characteristics of human mesenchymal stem cells derived from exfoliated deciduous teeth, bone marrow, gingival tissue, and umbilical cord[J]. Mol Med Rep, 2018, 18(6): 4969-4977.
[21] Ankrum JA, Ong JF, Karp JM.Mesenchymal stem cells: immune evasive, not immune privileged[J]. Nat Biotechnol, 2014, 32(3): 252-260.
[22] Nauta AJ, Fibbe WE.Immunomodulatory properties of mesenchymal stromal cells[J]. Blood, 2007, 110(10): 3499-3506.
[23] Koç ON, Day J, Nieder M, et al.Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH)[J]. Bone Marrow Transplant, 2002, 30(4): 215-222.
[24] Pinheiro D, Dias I, Freire T, et al.Effects of mesenchymal stem cells conditioned medium treatment in mice with cholestatic liver fibrosis[J]. Life Sci, 2021, 281: 119768.
[25] Khoury M, Cuenca J, Cruz FF, et al.Current status of cell-based therapies for respiratory virus infections: applicability to COVID-19[J]. Eur Respir J, 2020, 55(6): 2000858.
[26] Chan MC, Kuok DI, Leung CY, et al.Human mesenchymal stromalcells reduce influenza A H5N1-associated acute lung injury in vitroand in vivo[J]. Proc Natl Acad Sci USA, 2016, 113(13): 3621-3626.
[27] Li Y, Xu J, Shi W, et al.Mesenchymal stromal cell treatment prevents H9N2 avian influenza virus-induced acute lung injury in mice[J]. Stem Cell Res Ther, 2016, 7(1): 159.
[28] Chen J, Hu C, Chen L, et al.Clinical study of mesenchymal stem cell treatment for acute respiratory distress syndrome induced by epidemic influenza A (H7N9) infection: a hint for COVID-19 treatment[J]. Engineering (Beijing), 2020, 6(10): 1153-1161.
[29] Neidlinger-Wilke C, Ekkerlein A, Goncalves RM, et al.Mesench-ymal stem cell secretome decreases the inflammatory response in annulus fibrosus organ cultures[J]. Eur Cell Mater, 2021, 41: 1-19.
[30] English K.Mechanisms of mesenchymal stromal cell immunom-odulation[J]. Immunol Cell Biol,2013, 91(1): 19-26.
[31] Sohni A, Verfaillie CM.Mesenchymal stem cells migration homing and tracking[J]. Stem Cells Int, 2013: 130763.
[32] Meng F, Xu R, Wang S, et al.Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19: a phase 1 clinical trial[J]. Signal Transduct Target Ther, 2020, 5(1): 172.
[33] Leng Z, Zhu R, Hou W, et al.Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 Pneumonia[J]. Aging Dis, 2020, 11(2): 216-228.
[34] Chen L, Zhang W, Yue H, et al.Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells[J]. Stem Cells Dev, 2007, 16(5): 719-731.
[35] Zhang B, Liu R, Shi D, et al.Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population[J]. Blood, 2009, 113(1): 46-57.
[36] Shi X, Mao J, Liu Y.Pulp stem cells derived from human permanent and deciduous teeth: Biological characteristics and therapeutic applications[J]. Stem Cells Transl Med, 2020, 9(4): 445-464.
[37] Yeo RW, Lai RC, Zhang B, et al.Mesenchymal stem cell: an efficient mass producer of exosomes for drug delivery[J]. Adv Drug Deliv Rev, 2013, 65(3): 336-341.
[38] Kim HS, Choi DY, Yun SJ, et al.Proteomicanalysis of microvesicles derived from human mesenchymal stem cells[J]. J Proteome Res, 2012, 11(2): 839-849.
[39] Phinney DG, Di Giuseppe M, Njah J, et al.Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs[J]. Nat Commun, 2015, 6: 8472.
[40] Zhu YG, Feng XM, Abbott J, et al.Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice[J]. Stem Cells, 2014, 32(1): 116-125.
[41] Jia Y, Lu T, Chen Q, et al.Exosomes secreted from sonic hedgehog-modified bone mesenchymal stem cells facilitate the repair of rat spinal cord injuries[J]. Acta Neurochir (Wien), 2021, 163(8): 2297-2306.
[42] Zhang E, Geng X, Shan S, et al.Exosomes derived from bone marrow mesenchymal stem cells reverse epithelial-mesenchymal transition potentially via attenuating Wnt/β-catenin signaling to alleviate silica-induced pulmonary fibrosis[J]. Toxicol Mech Methods, 2021, 5: 1-40.
[43] Lee RH, Pulin AA, Seo MJ, et al.Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6[J]. Cell Stem Cell, 2009, 5(1): 54-63.
[44] Qian X, Xu C, Fang S, et al.Exosomal micrornas derived from umbilical mesenchymal stem cells inhibit hepatitis cvirus infection[J]. Stem Cells Transl Med, 2016, 5(9): 1190-1203.
[45] Liang B, Chen J, Li T, et al.Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells: A case report[J]. Medicine (Baltimore), 2020, 99(31): e21429.