Abstract
Coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 with severe respiratory failure and organ damage that later appeared as a pandemic disease. Worldwide, people’s mental and physical health and socioeconomic have been affected. Currently, with no promising treatment for COVID-19, the existing anti-viral drugs and vaccines are the only hope to boost the host immune system to reduce morbidity and mortality rate. Unfortunately, several reports show that people who are partially or fully vaccinated are still susceptible to COVID-19 infection. Evidence suggests that COVID-19 immunopathology may include dysregulation of macrophages and monocytes, reduced type 1 interferons (IFN-1), and enhanced cytokine storm that results in hypersecretion of proinflammatory cytokines, capillary leak syndrome, intravascular coagulation, and acute respiratory distress syndrome (ARDS) ultimately leading to the worsening of patient’s condition and death in most cases. The recent use of cell-based therapies such as mesenchymal stem cells (MSCs) for critically ill COVID-19 patients has been authorized by the Food and Drug Administration (FDA) to alleviate cytokine release syndrome. It protects the alveolar epithelial cells by promoting immunomodulatory action and secreting therapeutic exosomes to improve lung function and attenuate respiratory failure. As a result, multiple clinical trials have been registered using MSCs that aim to use various cell sources, and dosages to promote safety and efficacy against COVID-19 infection. In this review, the possibility of using MSCs in COVID-19 treatment and its associated challenges in their use have been briefly discussed.
Keywords: Mesenchymal stem cells, COVID-19, tissue regeneration, immunomodulation, cytokine storm, exosomes.
[http://dx.doi.org/10.3906/sag-2004-168] [PMID: 32299202]
[http://dx.doi.org/10.1038/nature02145] [PMID: 14647384]
[http://dx.doi.org/10.1016/j.lfs.2020.118568] [PMID: 33035589]
[http://dx.doi.org/10.1016/S0140-6736(20)30251-8] [PMID: 32007145]
[http://dx.doi.org/10.1038/s41586-020-2951-z] [PMID: 33199918]
[http://dx.doi.org/10.1080/25765299.2020.1836812]
[http://dx.doi.org/10.3390/life10080146] [PMID: 32784922]
[http://dx.doi.org/10.1007/s40495-020-00229-2] [PMID: 32837855]
[http://dx.doi.org/10.1186/s12931-021-01628-9] [PMID: 33514373]
[http://dx.doi.org/10.3389/fphar.2021.664349] [PMID: 34163357]
[http://dx.doi.org/10.1016/j.jhep.2020.04.006] [PMID: 32298767]
[http://dx.doi.org/10.1089/scd.2020.0122] [PMID: 33307968]
[http://dx.doi.org/10.1080/14712598.2020.1689954] [PMID: 31701782]
[http://dx.doi.org/10.1002/adhm.202001689] [PMID: 33433956]
[http://dx.doi.org/10.1038/s41536-019-0083-6] [PMID: 31815001]
[http://dx.doi.org/10.1002/cbin.11440] [PMID: 32767687]
[http://dx.doi.org/10.4103/JNSM.JNSM]
[http://dx.doi.org/10.1016/j.coviro.2011.10.008] [PMID: 22328912]
[http://dx.doi.org/10.1146/annurev-virology-031413-085537] [PMID: 25599080]
[http://dx.doi.org/10.18632/aging.102314] [PMID: 31575829]
[http://dx.doi.org/10.1016/j.imlet.2015.05.020] [PMID: 26051681]
[http://dx.doi.org/10.1186/s13287-016-0395-z] [PMID: 27793190]
[http://dx.doi.org/10.1155/2016/4285215] [PMID: 26823669]
[http://dx.doi.org/10.1038/nri2395] [PMID: 19172693]
[http://dx.doi.org/10.1016/S0140-6736(08)60690-X] [PMID: 18468541]
[http://dx.doi.org/10.1186/1478-811X-9-12] [PMID: 21569606]
[http://dx.doi.org/10.1016/j.stem.2009.02.001] [PMID: 19265660]
[http://dx.doi.org/10.1002/jcb.20886] [PMID: 16619257]
[http://dx.doi.org/10.1002/biof.1587] [PMID: 31755595]
[http://dx.doi.org/10.14336/AD.2020.0228] [PMID: 32257537]
[http://dx.doi.org/10.1134/S0006297920120068] [PMID: 33705292]
[http://dx.doi.org/10.1002/art.39477] [PMID: 26474311]
[http://dx.doi.org/10.1016/j.jcyt.2016.09.008] [PMID: 27769637]
[http://dx.doi.org/10.1007/s13238-017-0498-z] [PMID: 29302861]
[http://dx.doi.org/10.1186/s13287-019-1518-0]
[http://dx.doi.org/10.1016/S0377-1237(17)30954-1] [PMID: 28769276]
[http://dx.doi.org/10.1002/sctm.20-0118] [PMID: 32896982]
[http://dx.doi.org/10.1016/j.lfs.2020.118588] [PMID: 33049279]
[http://dx.doi.org/10.1186/s13287-020-01849-7] [PMID: 32948252]
[http://dx.doi.org/10.1002/iub.2387] [PMID: 33006813]
[http://dx.doi.org/10.1016/j.btre.2020.e00467] [PMID: 32420049]
[http://dx.doi.org/10.1016/j.cellimm.2011.06.014] [PMID: 21757189]
[http://dx.doi.org/10.1007/BF02256058] [PMID: 12595759]
[http://dx.doi.org/10.1007/s00395-011-0221-9] [PMID: 21901289]
[http://dx.doi.org/10.3727/096368910X508762] [PMID: 20525442]
[http://dx.doi.org/10.1016/S2213-2600(20)30216-2] [PMID: 32353251]
[http://dx.doi.org/10.1073/pnas.1400593111] [PMID: 24572573]
[http://dx.doi.org/10.1128/MMBR.05015-11] [PMID: 22390970]
[http://dx.doi.org/10.4081/itjm.2020.1401]
[http://dx.doi.org/10.1186/s12985-021-01588-y] [PMID: 34088317]
[http://dx.doi.org/10.1016/j.cyto.2021.155428] [PMID: 33550165]
[http://dx.doi.org/10.3389/fimmu.2021.666223] [PMID: 34046036]
[http://dx.doi.org/10.1098/rsob.200160] [PMID: 32961074]
[http://dx.doi.org/10.1016/j.tmaid.2020.101755] [PMID: 32479816]
[http://dx.doi.org/10.1007/s40618-021-01506-7] [PMID: 33559848]
[http://dx.doi.org/10.1186/1471-2172-6-2] [PMID: 15655079]
[http://dx.doi.org/10.1371/journal.ppat.1007390] [PMID: 30571771]
[http://dx.doi.org/10.1080/00325481.2020.1855921] [PMID: 33245005]
[http://dx.doi.org/10.1016/j.cytogfr.2020.12.005] [PMID: 33573850]
[http://dx.doi.org/10.3390/pathogens10050565] [PMID: 34066983]
[http://dx.doi.org/10.3390/vaccines9050436] [PMID: 33946736]
[http://dx.doi.org/10.3389/fpubh.2021.671788] [PMID: 34109148]
[http://dx.doi.org/10.1016/j.bbadis.2020.166014]
[http://dx.doi.org/10.1016/j.medidd.2020.100019] [PMID: 32296777]
[http://dx.doi.org/10.1016/j.intimp.2021.107694] [PMID: 33932694]
[http://dx.doi.org/10.4049/jimmunol.1701135] [PMID: 28923980]
[http://dx.doi.org/10.1080/08830185.2020.1844195] [PMID: 33191813]
[http://dx.doi.org/10.14336/AD.2020.1218] [PMID: 33815870]
[http://dx.doi.org/10.1007/s12015-018-9817-x] [PMID: 29687338]
[http://dx.doi.org/10.1186/s12964-021-00730-1] [PMID: 33892745]
[http://dx.doi.org/10.14336/AD.2020.0301] [PMID: 32257554]
[http://dx.doi.org/10.2147/IJN.S225453] [PMID: 32009783]
[http://dx.doi.org/10.3390/pharmaceutics13060768] [PMID: 34064144]
[http://dx.doi.org/10.3390/nano11061481]
[http://dx.doi.org/10.4149/neo_2017_601] [PMID: 28895404]
[http://dx.doi.org/10.4252/wjsc.v13.i1.49]
[http://dx.doi.org/10.1080/20013078.2020.1795365] [PMID: 32944185]
[http://dx.doi.org/10.1016/j.yexcr.2019.111596] [PMID: 27756608]
[http://dx.doi.org/10.1038/sigtrans.2017.23] [PMID: 27718095]
[http://dx.doi.org/10.1002/stem.2551]
[http://dx.doi.org/10.3390/jcm10040711] [PMID: 33670202]
[http://dx.doi.org/10.1089/scd.2020.0080] [PMID: 32380908]
[http://dx.doi.org/10.1017/S0950268820001557] [PMID: 32641174]
[http://dx.doi.org/10.3389/fimmu.2020.02160] [PMID: 32983180]
[http://dx.doi.org/10.1016/j.biopha.2021.111518] [PMID: 33774315]
[http://dx.doi.org/10.1016/j.ejphar.2020.173549] [PMID: 32926916]
[http://dx.doi.org/10.1016/j.imu.2021.100526] [PMID: 33869730]
[http://dx.doi.org/10.1016/j.crphar.2021.100042] [PMID: 34870150]
[http://dx.doi.org/10.1002/adtp.202000034] [PMID: 32838027]
[http://dx.doi.org/10.1038/s41467-020-18685-1] [PMID: 33037212]
[http://dx.doi.org/10.1148/ryai.2020200098] [PMID: 33928257]
[http://dx.doi.org/10.1016/j.jcyt.2018.10.008] [PMID: 30503100]
[http://dx.doi.org/10.3389/fphar.2021.647652]
[http://dx.doi.org/10.21203/rs.3.rs-370545/v1]
[http://dx.doi.org/10.3389/fimmu.2021.631291] [PMID: 33763076]
[http://dx.doi.org/10.1155/2018/3057624] [PMID: 30013600]
[http://dx.doi.org/10.1007/s12015-020-09973-w] [PMID: 32281052]
[http://dx.doi.org/10.1073/pnas.2004168117] [PMID: 32253318]
[http://dx.doi.org/10.1186/s13287-020-01802-8] [PMID: 32678017]
[http://dx.doi.org/10.1155/2021/6666370] [PMID: 34035820]
[http://dx.doi.org/10.1155/2020/1939768] [PMID: 33274176]
[http://dx.doi.org/10.1186/s13287-020-01804-6] [PMID: 32698898]
[http://dx.doi.org/10.1007/s13238-020-00738-2] [PMID: 32519302]
[http://dx.doi.org/10.1016/j.blre.2020.100742] [PMID: 32854985]
[http://dx.doi.org/10.1177/0963689721995455] [PMID: 33650894]
[http://dx.doi.org/10.3389/fimmu.2020.01091] [PMID: 32574263]
[http://dx.doi.org/10.1155/2019/4236973] [PMID: 31191672]
[http://dx.doi.org/10.3389/fimmu.2013.00201] [PMID: 24027567]
[http://dx.doi.org/10.1146/annurev-bioeng-070909-105309] [PMID: 20415588]
[http://dx.doi.org/10.1126/sciadv.aba6884] [PMID: 32832666]
[http://dx.doi.org/10.1186/s13045-021-01037-x] [PMID: 33579329]
[http://dx.doi.org/10.1016/j.omtm.2019.05.004] [PMID: 31236426]
[http://dx.doi.org/10.15283/ijsc.2008.1.1.1] [PMID: 24855503]
[http://dx.doi.org/10.3389/fimmu.2019.01645] [PMID: 31417542]
[http://dx.doi.org/10.1016/j.molmed.2018.12.006] [PMID: 30711482]
[http://dx.doi.org/10.1097/MBC.0b013e3282ef99f6] [PMID: 17982314]
[http://dx.doi.org/10.3389/fimmu.2020.01338] [PMID: 32670295]
[http://dx.doi.org/10.18295/squmj.2018.18.03.002] [PMID: 30607265]