Mesenchymal Stem Cell Derived-Exosomes as Effective Factors in Reducing Cytokine Storm Symptoms of COVID-19

Author(s): Amir Hossein Kheirkhah, Seyed Hossein Shahcheraghi, Malihe lotfi, Marzieh lotfi*, Sanaz Raeisi, Zulfiqar Mirani*

Journal Name: Protein & Peptide Letters

Volume 28 , Issue 8 , 2021


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Abstract:

Given that conventional therapies are ineffective for COVID-19, obtained exosomes from stem cells have been proposed as a sustainable and effective treatment. Exosomes are subsets with lengths between 30 and 100 nanometers, and they can be secreted by different cells. Exosomes are containing different types of miRNAs, mRNAs, and different proteins. The role of immune system modulation of exosomes of mesenchymal stem cells has been studied and confirmed in more than one study. Exosome miRNAs detect and reduce cytokines that cause cytokine storms such as IL-7, IL-2, IL-6, etc. These miRNAs include miR-21, miR-24, miR-124, miR-145, etc. The risks associated with treatment with exosomes from different cells are relatively small compared to other treatments because transplanted cells do not stimulate the host immune system and also has reduced infection transmission. Due to the ineffectiveness of existing drugs in reducing inflammation and preventing cytokine storms, the use of immune-boosting systems may be suggested as another way to control cytokine storm.

Keywords: Exosome, COVID-19, SARS-CoV-2, miRNA, cytokine storm, immune system.

[1]
Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; Niu, P.; Zhan, F.; Ma, X.; Wang, D.; Xu, W.; Wu, G.; Gao, G.F.; Tan, W. A novel coronavirus from patients with pneumonia in China, 2019. N. Engl. J. Med., 2020, 382(8), 727-733.
[http://dx.doi.org/10.1056/NEJMoa2001017] [PMID: 31978945]
[2]
Corman, V.M.; Landt, O.; Kaiser, M.; Molenkamp, R.; Meijer, A.; Chu, D.K.; Bleicker, T.; Brünink, S.; Schneider, J.; Schmidt, M.L.; Mulders, D.G.; Haagmans, B.L.; van der Veer, B.; van den Brink, S.; Wijsman, L.; Goderski, G.; Romette, J.L.; Ellis, J.; Zambon, M.; Peiris, M.; Goossens, H.; Reusken, C.; Koopmans, M.P.; Drosten, C. Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. Euro Surveill., 2020, 25(3), 2000045.
[http://dx.doi.org/10.2807/1560-7917.ES.2020.25.3.2000045] [PMID: 31992387]
[3]
Chen, N.; Zhou, M.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; Wei, Y.; Xia, J.; Yu, T.; Zhang, X.; Zhang, L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020, 395(10223), 507-513.
[http://dx.doi.org/10.1016/S0140-6736(20)30211-7] [PMID: 32007143]
[4]
Channappanavar, R.; Perlman, S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol., 2017, 39(5), 529-539.
[http://dx.doi.org/10.1007/s00281-017-0629-x]
[5]
Cameron, M.J.; Bermejo-Martin, J.F.; Danesh, A.; Muller, M.P.; Kelvin, D.J. Human immunopathogenesis of severe acute respiratory syndrome (SARS). Virus Res., 2008, 133(1), 13-19.
[http://dx.doi.org/10.1016/j.virusres.2007.02.014] [PMID: 17374415]
[6]
Min, C-K.; Cheon, S.; Ha, N-Y.; Sohn, K.M.; Kim, Y.; Aigerim, A.; Shin, H.M.; Choi, J-Y.; Inn, K-S.; Kim, J-H.; Moon, J.Y.; Choi, M.S.; Cho, N.H.; Kim, Y.S. Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci. Rep., 2016, 6(1), 25359.
[http://dx.doi.org/10.1038/srep25359] [PMID: 27146253]
[7]
Heo, J.S. Chondrogenic differentiation of human mesenchymal stem cells on a patterned polymer surface. Korean J. Lab. Med., 2015, 47(3), 117-124.
[8]
Wang, L-T.; Ting, C-H.; Yen, M-L.; Liu, K-J.; Sytwu, H-K.; Wu, K.K.; Yen, B.L. Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials. J. Biomed. Sci., 2016, 23(1), 76.
[http://dx.doi.org/10.1186/s12929-016-0289-5] [PMID: 27809910]
[9]
Sengupta, V.; Sengupta, S.; Lazo, A.; Woods, P.; Nolan, A.; Bremer, N. Exosomes derived from bone marrow mesenchymal stem cells as treatment for severe COVID-19. Stem Cells Dev., 2020.
[http://dx.doi.org/10.1089/scd.2020.0080]
[10]
Pan, B-T.; Johnstone, R.M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell, 1983, 33(3), 967-978.
[http://dx.doi.org/10.1016/0092-8674(83)90040-5] [PMID: 6307529]
[11]
Théry, C.; Zitvogel, L.; Amigorena, S. Exosomes: composition, biogenesis and function. Nat. Rev. Immunol., 2002, 2(8), 569-579.
[http://dx.doi.org/10.1038/nri855] [PMID: 12154376]
[12]
Vlassov, A.V.; Magdaleno, S.; Setterquist, R.; Conrad, R. Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim. Biophys. Acta, 2012, 1820(7), 940-948.
[http://dx.doi.org/10.1016/j.bbagen.2012.03.017] [PMID: 22503788]
[13]
van der Pol, E.; Böing, A.N.; Harrison, P.; Sturk, A.; Nieuwland, R. Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol. Rev., 2012, 64(3), 676-705.
[http://dx.doi.org/10.1124/pr.112.005983] [PMID: 22722893]
[14]
Ha, D.; Yang, N.; Nadithe, V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm. Sin. B, 2016, 6(4), 287-296.
[http://dx.doi.org/10.1016/j.apsb.2016.02.001] [PMID: 27471669]
[15]
Hosoki, K.; Chakraborty, A.; Sur, S. Molecular mechanisms and epidemiology of COVID-19 from an allergist’s perspective. J. Allergy Clin. Immunol., 2020, 146(2), 285-299.
[http://dx.doi.org/10.1016/j.jaci.2020.05.033] [PMID: 32624257]
[16]
Moore, J.B.; June, C.H. Cytokine release syndrome in severe COVID-19. Science, 2020, 368(6490), 473-474.
[http://dx.doi.org/10.1126/science.abb8925] [PMID: 32303591]
[17]
Hui, D.S.; I Azhar, E.; Madani, T.A.; Ntoumi, F.; Kock, R.; Dar, O.; Ippolito, G.; Mchugh, T.D.; Memish, Z.A.; Drosten, C.; Zumla, A.; Petersen, E. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health - The latest 2019 novel coronavirus outbreak in Wuhan, China. Int. J. Infect. Dis., 2020, 91, 264-266.
[http://dx.doi.org/10.1016/j.ijid.2020.01.009] [PMID: 31953166]
[18]
Sahin, A.R.; Erdogan, A.; Agaoglu, P.M.; Dineri, Y.; Cakirci, A.Y.; Senel, M.E.; Okyay, R.A.; Tasdogan, A.M. 2019 novel coronavirus (COVID-19) outbreak: a review of the current literature. Eurasian j. med. oncol, 2020, 4(1), 1-7.
[19]
Leung, W.K.; To, K.F.; Chan, P.K.; Chan, H.L.; Wu, A.K.; Lee, N.; Yuen, K.Y.; Sung, J.J. Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection. Gastroenterology, 2003, 125(4), 1011-1017.
[http://dx.doi.org/10.1016/j.gastro.2003.08.001] [PMID: 14517783]
[20]
Wang, D.; Hu, B.; Hu, C.; Zhu, F.; Liu, X.; Zhang, J.; Wang, B.; Xiang, H.; Cheng, Z.; Xiong, Y.; Zhao, Y.; Li, Y.; Wang, X.; Peng, Z. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. JAMA, 2020, 323(11), 1061-1069.
[http://dx.doi.org/10.1001/jama.2020.1585] [PMID: 32031570]
[21]
Li, H.; Wang, Y.M.; Xu, J.Y.; Cao, B. Potential antiviral therapeutics for 2019 Novel Coronavirus. Zhonghua Jie He He Hu Xi Za Zhi, 2020, 43(0), E002.
[PMID: 32023685]
[22]
Wu, C.; Chen, X.; Cai, Y.; Zhou, X.; Xu, S.; Huang, H.; Zhang, L.; Zhou, X.; Du, C.; Zhang, Y. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med, 2020.
[23]
Stockman, L.J.; Bellamy, R.; Garner, P. SARS: systematic review of treatment effects. PLoS Med., 2006, 3(9), e343.
[http://dx.doi.org/10.1371/journal.pmed.0030343] [PMID: 16968120]
[24]
Fung, T.S.; Liu, D.X. Coronavirus infection, ER stress, apoptosis and innate immunity. Front. Microbiol., 2014, 5, 296.
[http://dx.doi.org/10.3389/fmicb.2014.00296] [PMID: 24987391]
[25]
Savarino, A.; Boelaert, J.R.; Cassone, A.; Majori, G.; Cauda, R. Effects of chloroquine on viral infections: an old drug against today’s diseases? Lancet Infect. Dis., 2003, 3(11), 722-727.
[http://dx.doi.org/10.1016/S1473-3099(03)00806-5] [PMID: 14592603]
[26]
Zhou, D.; Dai, S-M.; Tong, Q. COVID-19: a recommendation to examine the effect of hydroxychloroquine in preventing infection and progression. J. Antimicrob. Chemother., 2020, 75(7), 1667-1670.
[http://dx.doi.org/10.1093/jac/dkaa114] [PMID: 32196083]
[27]
Devaux, C.A.; Rolain, J-M.; Colson, P.; Raoult, D. New insights on the antiviral effects of chloroquine against coronavirus: what to expect for COVID-19? Int. J. Antimicrob. Agents, 2020, 55(5), 105938.
[http://dx.doi.org/10.1016/j.ijantimicag.2020.105938] [PMID: 32171740]
[28]
Cao, B.; Wang, Y.; Wen, D.; Liu, W.; Wang, J.; Fan, G.; Ruan, L.; Song, B.; Cai, Y.; Wei, M.; Li, X.; Xia, J.; Chen, N.; Xiang, J.; Yu, T.; Bai, T.; Xie, X.; Zhang, L.; Li, C.; Yuan, Y.; Chen, H.; Li, H.; Huang, H.; Tu, S.; Gong, F.; Liu, Y.; Wei, Y.; Dong, C.; Zhou, F.; Gu, X.; Xu, J.; Liu, Z.; Zhang, Y.; Li, H.; Shang, L.; Wang, K.; Li, K.; Zhou, X.; Dong, X.; Qu, Z.; Lu, S.; Hu, X.; Ruan, S.; Luo, S.; Wu, J.; Peng, L.; Cheng, F.; Pan, L.; Zou, J.; Jia, C.; Wang, J.; Liu, X.; Wang, S.; Wu, X.; Ge, Q.; He, J.; Zhan, H.; Qiu, F.; Guo, L.; Huang, C.; Jaki, T.; Hayden, F.G.; Horby, P.W.; Zhang, D.; Wang, C. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N. Engl. J. Med., 2020, 382(19), 1787-1799.
[http://dx.doi.org/10.1056/NEJMoa2001282] [PMID: 32187464]
[29]
Agostini, M.L.; Andres, E.L.; Sims, A.C.; Graham, R.L.; Sheahan, T.P.; Lu, X.; Smith, E.C.; Case, J.B.; Feng, J.Y.; Jordan, R.; Ray, A.S.; Cihlar, T.; Siegel, D.; Mackman, R.L.; Clarke, M.O.; Baric, R.S.; Denison, M.R. Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease. MBio, 2018, 9(2), e00221-18.
[http://dx.doi.org/10.1128/mBio.00221-18] [PMID: 29511076]
[30]
Wang, M.; Cao, R.; Zhang, L.; Yang, X.; Liu, J.; Xu, M.; Shi, Z.; Hu, Z.; Zhong, W.; Xiao, G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res., 2020, 30(3), 269-271.
[http://dx.doi.org/10.1038/s41422-020-0282-0] [PMID: 32020029]
[31]
Crestani, B.; Cornillet, P.; Dehoux, M.; Rolland, C.; Guenounou, M.; Aubier, M. Alveolar type II epithelial cells produce interleukin-6 in vitro and in vivo. Regulation by alveolar macrophage secretory products. J. Clin. Invest., 1994, 94(2), 731-740.
[http://dx.doi.org/10.1172/JCI117392] [PMID: 8040328]
[32]
Kang, S.; Tanaka, T.; Narazaki, M.; Kishimoto, T. Targeting interleukin-6 signaling in clinic. Immunity, 2019, 50(4), 1007-1023.
[http://dx.doi.org/10.1016/j.immuni.2019.03.026] [PMID: 30995492]
[33]
Nishimoto, N.; Terao, K.; Mima, T.; Nakahara, H.; Takagi, N.; Kakehi, T. Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease. Blood, 2008, 112(10), 3959-3964.
[http://dx.doi.org/10.1182/blood-2008-05-155846] [PMID: 18784373]
[34]
Khamitov, R.A.; Loginova, S.Ia.; Shchukina, V.N.; Borisevich, S.V.; Maksimov, V.A.; Shuster, A.M. Antiviral activity of arbidol and its derivatives against the pathogen of severe acute respiratory syndrome in the cell cultures. Vopr. Virusol., 2008, 53(4), 9-13.
[PMID: 18756809]
[35]
Kadam, R.U.; Wilson, I.A. Structural basis of influenza virus fusion inhibition by the antiviral drug Arbidol. Proc. Natl. Acad. Sci. USA, 2017, 114(2), 206-214.
[http://dx.doi.org/10.1073/pnas.1617020114] [PMID: 28003465]
[36]
Zhou, B.; Zhong, N.; Guan, Y. Treatment with convalescent plasma for influenza A (H5N1) infection. N. Engl. J. Med., 2007, 357(14), 1450-1451.
[http://dx.doi.org/10.1056/NEJMc070359] [PMID: 17914053]
[37]
Hung, I.F.; To, K.K.; Lee, C-K.; Lee, K-L.; Chan, K.; Yan, W-W.; Liu, R.; Watt, C-L.; Chan, W-M.; Lai, K-Y.; Koo, C.K.; Buckley, T.; Chow, F.L.; Wong, K.K.; Chan, H.S.; Ching, C.K.; Tang, B.S.; Lau, C.C.; Li, I.W.; Liu, S.H.; Chan, K.H.; Lin, C.K.; Yuen, K.Y. Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin. Infect. Dis., 2011, 52(4), 447-456.
[http://dx.doi.org/10.1093/cid/ciq106] [PMID: 21248066]
[38]
Duan, K.; Liu, B.; Li, C.; Zhang, H.; Yu, T.; Qu, J.; Zhou, M.; Chen, L.; Meng, S.; Hu, Y.; Peng, C.; Yuan, M.; Huang, J.; Wang, Z.; Yu, J.; Gao, X.; Wang, D.; Yu, X.; Li, L.; Zhang, J.; Wu, X.; Li, B.; Xu, Y.; Chen, W.; Peng, Y.; Hu, Y.; Lin, L.; Liu, X.; Huang, S.; Zhou, Z.; Zhang, L.; Wang, Y.; Zhang, Z.; Deng, K.; Xia, Z.; Gong, Q.; Zhang, W.; Zheng, X.; Liu, Y.; Yang, H.; Zhou, D.; Yu, D.; Hou, J.; Shi, Z.; Chen, S.; Chen, Z.; Zhang, X.; Yang, X. Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc. Natl. Acad. Sci. USA, 2020, 117(17), 9490-9496.
[http://dx.doi.org/10.1073/pnas.2004168117] [PMID: 32253318]
[39]
Thompson, B.T. Glucocorticoids and acute lung injury. Crit. Care Med., 2003, 31(4)(Suppl.), S253-S257.
[http://dx.doi.org/10.1097/01.CCM.0000057900.19201.55] [PMID: 12682449]
[40]
Yang, X.; Yu, Y.; Xu, J.; Shu, H.; Xia, J.; Liu, H.; Wu, Y.; Zhang, L.; Yu, Z.; Fang, M.; Yu, T.; Wang, Y.; Pan, S.; Zou, X.; Yuan, S.; Shang, Y. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir. Med., 2020, 8(5), 475-481.
[http://dx.doi.org/10.1016/S2213-2600(20)30079-5] [PMID: 32105632]
[41]
Siddiqi, H.K.; Mehra, M.R. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal. J. Heart Lung Transplant., 2020, 39(5), 405-407.
[http://dx.doi.org/10.1016/j.healun.2020.03.012] [PMID: 32362390]
[42]
Sanders, J.M.; Monogue, M.L.; Jodlowski, T.Z.; Cutrell, J.B. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review. JAMA, 2020, 323(18), 1824-1836.
[http://dx.doi.org/10.1001/jama.2020.6019] [PMID: 32282022]
[43]
Prompetchara, E.; Ketloy, C.; Palaga, T. Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic. Asian Pac. J. Allergy Immunol., 2020, 38(1), 1-9.
[PMID: 32105090]
[44]
Frieman, M.; Heise, M.; Baric, R. SARS coronavirus and innate immunity. Virus Res., 2008, 133(1), 101-112.
[http://dx.doi.org/10.1016/j.virusres.2007.03.015] [PMID: 17451827]
[45]
Liu, L.; Wei, Q.; Nishiura, K.; Peng, J.; Wang, H.; Midkiff, C.; Alvarez, X.; Qin, C.; Lackner, A.; Chen, Z. Spatiotemporal interplay of severe acute respiratory syndrome coronavirus and respiratory mucosal cells drives viral dissemination in rhesus macaques. Mucosal Immunol., 2016, 9(4), 1089-1101.
[http://dx.doi.org/10.1038/mi.2015.127] [PMID: 26647718]
[46]
Thiel, V.; Weber, F. Interferon and cytokine responses to SARS-coronavirus infection. Cytokine Growth Factor Rev., 2008, 19(2), 121-132.
[http://dx.doi.org/10.1016/j.cytogfr.2008.01.001] [PMID: 18321765]
[47]
Zhang, W.; Zhao, Y.; Zhang, F.; Wang, Q.; Li, T.; Liu, Z.; Wang, J.; Qin, Y.; Zhang, X.; Yan, X.; Zeng, X.; Zhang, S. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the Perspectives of clinical immunologists from China. Clin. Immunol., 2020, 214, 108393.
[http://dx.doi.org/10.1016/j.clim.2020.108393] [PMID: 32222466]
[48]
Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; Cheng, Z.; Yu, T.; Xia, J.; Wei, Y.; Wu, W.; Xie, X.; Yin, W.; Li, H.; Liu, M.; Xiao, Y.; Gao, H.; Guo, L.; Xie, J.; Wang, G.; Jiang, R.; Gao, Z.; Jin, Q.; Wang, J.; Cao, B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 2020, 395(10223), 497-506.
[http://dx.doi.org/10.1016/S0140-6736(20)30183-5] [PMID: 31986264]
[49]
Liu, W.J.; Zhao, M.; Liu, K.; Xu, K.; Wong, G.; Tan, W.; Gao, G.F. T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV. Antiviral Res., 2017, 137, 82-92.
[http://dx.doi.org/10.1016/j.antiviral.2016.11.006] [PMID: 27840203]
[50]
Lessler, J.; Reich, N.G.; Brookmeyer, R.; Perl, T.M.; Nelson, K.E.; Cummings, D.A. Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect. Dis., 2009, 9(5), 291-300.
[http://dx.doi.org/10.1016/S1473-3099(09)70069-6] [PMID: 19393959]
[51]
Kindler, E.; Thiel, V.; Weber, F. Interaction of SARS and MERS coronaviruses with the antiviral interferon response. Adv. Virus Res., 2016, 96, 219-243.
[http://dx.doi.org/10.1016/bs.aivir.2016.08.006] [PMID: 27712625]
[52]
Kikkert, M. Innate immune evasion by human respiratory RNA viruses. J. Innate Immun., 2020, 12(1), 4-20.
[http://dx.doi.org/10.1159/000503030] [PMID: 31610541]
[53]
Faure, E.; Poissy, J.; Goffard, A.; Fournier, C.; Kipnis, E.; Titecat, M.; Bortolotti, P.; Martinez, L.; Dubucquoi, S.; Dessein, R.; Gosset, P.; Mathieu, D.; Guery, B. Distinct immune response in two MERS-CoV-infected patients: can we go from bench to bedside? PLoS One, 2014, 9(2), e88716.
[http://dx.doi.org/10.1371/journal.pone.0088716] [PMID: 24551142]
[54]
Mosaddeghi, P.; Negahdaripour, M.; Dehghani, Z.; Farahmandnejad, M.; Moghadami, M.; Nezafat, N.; Masoompour, S. M. Therapeutic approaches for COVID-19 based on the dynamics of interferon-mediated immune responses. Curr. Signal Transduct. Ther., 2020. [Epub Ahead of Print]
[55]
Golchin, A.; Farahany, T.Z.; Khojasteh, A.; Soleimanifar, F.; Ardeshirylajimi, A. The clinical trials of mesenchymal stem cell therapy in skin diseases: an update and concise review. Curr. Stem Cell Res. Ther., 2019, 14(1), 22-33.
[http://dx.doi.org/10.2174/1574888X13666180913123424] [PMID: 30210006]
[56]
Uccelli, A.; de Rosbo, N.K. The immunomodulatory function of mesenchymal stem cells: mode of action and pathways. Ann. N. Y. Acad. Sci., 2015, 1351(1), 114-126.
[http://dx.doi.org/10.1111/nyas.12815] [PMID: 26152292]
[57]
Liang, B.; Chen, J.; Li, T.; Wu, H.; Yang, W.; Li, Y.; Li, J.; Yu, C.; Nie, F.; Ma, Z.; Yang, M.; Xiao, M.; Nie, P.; Gao, Y.; Qian, C.; Hu, M. Clinical remission of a critically ill COVID-19 patient treated by human umbilical cord mesenchymal stem cells: A case report. Medicine (Baltimore), 2020, 99(31), e21429.
[http://dx.doi.org/10.1097/MD.0000000000021429] [PMID: 32756149]
[58]
Leng, Z.; Zhu, R.; Hou, W.; Feng, Y.; Yang, Y.; Han, Q.; Shan, G.; Meng, F.; Du, D.; Wang, S.; Fan, J.; Wang, W.; Deng, L.; Shi, H.; Li, H.; Hu, Z.; Zhang, F.; Gao, J.; Liu, H.; Li, X.; Zhao, Y.; Yin, K.; He, X.; Gao, Z.; Wang, Y.; Yang, B.; Jin, R.; Stambler, I.; Lim, L.W.; Su, H.; Moskalev, A.; Cano, A.; Chakrabarti, S.; Min, K.J.; Ellison-Hughes, G.; Caruso, C.; Jin, K.; Zhao, R.C. Transplantation of ACE2-mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis., 2020, 11(2), 216-228.
[http://dx.doi.org/10.14336/AD.2020.0228] [PMID: 32257537]
[59]
Metcalfe, S.M. Mesenchymal stem cells and management of COVID-19 pneumonia. Med Drug Discov., 2020, 5, 100019.
[http://dx.doi.org/10.1016/j.medidd.2020.100019] [PMID: 32296777]
[60]
Urbanelli, L.; Buratta, S.; Sagini, K.; Ferrara, G.; Lanni, M.; Emiliani, C. Exosome-based strategies for diagnosis and therapy. Recent Patents CNS Drug Discov., 2015, 10(1), 10-27.
[http://dx.doi.org/10.2174/1574889810666150702124059] [PMID: 26133463]
[61]
Kowal, J.; Tkach, M.; Théry, C. Biogenesis and secretion of exosomes. Curr. Opin. Cell Biol., 2014, 29, 116-125.
[http://dx.doi.org/10.1016/j.ceb.2014.05.004] [PMID: 24959705]
[62]
van Niel, G.; D’Angelo, G.; Raposo, G. Shedding light on the cell biology of extracellular vesicles. Nat. Rev. Mol. Cell Biol., 2018, 19(4), 213-228.
[http://dx.doi.org/10.1038/nrm.2017.125] [PMID: 29339798]
[63]
Tan, S.S.; Yin, Y.; Lee, T.; Lai, R.C.; Yeo, R.W.Y.; Zhang, B.; Choo, A.; Lim, S.K. Therapeutic MSC exosomes are derived from lipid raft microdomains in the plasma membrane. J. Extracell. Vesicles, 2013, 2(1), 22614.
[http://dx.doi.org/10.3402/jev.v2i0.22614]
[64]
Rana, S.; Yue, S.; Stadel, D.; Zöller, M. Toward tailored exosomes: the exosomal tetraspanin web contributes to target cell selection. Int. J. Biochem. Cell Biol., 2012, 44(9), 1574-1584.
[http://dx.doi.org/10.1016/j.biocel.2012.06.018] [PMID: 22728313]
[65]
Vabulas, R.M.; Raychaudhuri, S.; Hayer-Hartl, M.; Hartl, F.U. Protein folding in the cytoplasm and the heat shock response. Cold Spring Harb. Perspect. Biol., 2010, 2(12), a004390.
[http://dx.doi.org/10.1101/cshperspect.a004390] [PMID: 21123396]
[66]
Andreu, Z.; Yáñez-Mó, M. Tetraspanins in extracellular vesicle formation and function. Front. Immunol., 2014, 5, 442.
[http://dx.doi.org/10.3389/fimmu.2014.00442] [PMID: 25278937]
[67]
Conde-Vancells, J.; Rodriguez-Suarez, E.; Embade, N.; Gil, D.; Matthiesen, R.; Valle, M.; Elortza, F.; Lu, S.C.; Mato, J.M.; Falcon-Perez, J.M. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J. Proteome Res., 2008, 7(12), 5157-5166.
[http://dx.doi.org/10.1021/pr8004887] [PMID: 19367702]
[68]
Sharma, A.; Khatun, Z.; Shiras, A. Tumor exosomes: cellular postmen of cancer diagnosis and personalized therapy. Nanomedicine (Lond.), 2016, 11(4), 421-437.
[http://dx.doi.org/10.2217/nnm.15.210] [PMID: 26784674]
[69]
Laffey, J.G.; Matthay, M.A. Fifty years of research in ARDS. Cell-based therapy for acute respiratory distress syndrome. Biology and potential therapeutic value. Am. J. Respir. Crit. Care Med., 2017, 196(3), 266-273.
[http://dx.doi.org/10.1164/rccm.201701-0107CP] [PMID: 28306336]
[70]
Gupta, N.; Su, X.; Popov, B.; Lee, J.W.; Serikov, V.; Matthay, M.A. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J. Immunol., 2007, 179(3), 1855-1863.
[http://dx.doi.org/10.4049/jimmunol.179.3.1855] [PMID: 17641052]
[71]
Devaney, J.; Horie, S.; Masterson, C.; Elliman, S.; Barry, F.; O’Brien, T.; Curley, G.F.; O’Toole, D.; Laffey, J.G. Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat. Thorax, 2015, 70(7), 625-635.
[http://dx.doi.org/10.1136/thoraxjnl-2015-206813] [PMID: 25986435]
[72]
Lee, J.W.; Fang, X.; Gupta, N.; Serikov, V.; Matthay, M.A. Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc. Natl. Acad. Sci. USA, 2009, 106(38), 16357-16362.
[http://dx.doi.org/10.1073/pnas.0907996106] [PMID: 19721001]
[73]
Yang, K.; Wang, J.; Wu, M.; Li, M.; Wang, Y.; Huang, X. Mesenchymal stem cells detect and defend against gammaherpesvirus infection via the cGAS-STING pathway. Sci. Rep., 2015, 5(1), 7820.
[http://dx.doi.org/10.1038/srep07820] [PMID: 25592282]
[74]
Gao, F.; Chiu, S.M.; Motan, D.A.; Zhang, Z.; Chen, L.; Ji, H.L.; Tse, H.F.; Fu, Q-L.; Lian, Q. Mesenchymal stem cells and immunomodulation: current status and future prospects. Cell Death Dis., 2016, 7(1), e2062-e2062.
[http://dx.doi.org/10.1038/cddis.2015.327] [PMID: 26794657]
[75]
Mahmoudi, M.; Taghavi Farahabadi, M.; Hashemi, S.M. Exosomes: mediators of immune regulation. Immunoregulation, 2019, 2(1), 3-8.
[76]
Lo Cicero, A.; Stahl, P.D.; Raposo, G. Extracellular vesicles shuffling intercellular messages: for good or for bad. Curr. Opin. Cell Biol., 2015, 35, 69-77.
[http://dx.doi.org/10.1016/j.ceb.2015.04.013] [PMID: 26001269]
[77]
Shah, T.G.; Predescu, D.; Predescu, S. Mesenchymal stem cells-derived extracellular vesicles in acute respiratory distress syndrome: a review of current literature and potential future treatment options. Clin. Transl. Med., 2019, 8(1), 25.
[http://dx.doi.org/10.1186/s40169-019-0242-9] [PMID: 31512000]
[78]
Allan, D.; Tieu, A.; Lalu, M.; Burger, D. Mesenchymal stromal cell-derived extracellular vesicles for regenerative therapy and immune modulation: progress and challenges toward clinical application. Stem Cells Transl. Med., 2020, 9(1), 39-46.
[http://dx.doi.org/10.1002/sctm.19-0114] [PMID: 31411820]
[79]
Reiner, A.T.; Witwer, K.W.; van Balkom, B.W.M.; de Beer, J.; Brodie, C.; Corteling, R.L.; Gabrielsson, S.; Gimona, M.; Ibrahim, A.G.; de Kleijn, D.; Lai, C.P.; Lötvall, J.; Del Portillo, H.A.; Reischl, I.G.; Riazifar, M.; Salomon, C.; Tahara, H.; Toh, W.S.; Wauben, M.H.M.; Yang, V.K.; Yang, Y.; Yeo, R.W.Y.; Yin, H.; Giebel, B.; Rohde, E.; Lim, S.K. Concise review: developing best‐practice models for the therapeutic use of extracellular vesicles. Stem Cells Transl. Med., 2017, 6(8), 1730-1739.
[http://dx.doi.org/10.1002/sctm.17-0055] [PMID: 28714557]
[80]
Théry, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; Ayre, D.C.; Bach, J.M.; Bachurski, D.; Baharvand, H.; Balaj, L.; Baldacchino, S.; Bauer, N.N.; Baxter, A.A.; Bebawy, M.; Beckham, C.; Bedina Zavec, A.; Benmoussa, A.; Berardi, A.C.; Bergese, P.; Bielska, E.; Blenkiron, C.; Bobis-Wozowicz, S.; Boilard, E.; Boireau, W.; Bongiovanni, A.; Borràs, F.E.; Bosch, S.; Boulanger, C.M.; Breakefield, X.; Breglio, A.M.; Brennan, M.Á.; Brigstock, D.R.; Brisson, A.; Broekman, M.L.; Bromberg, J.F.; Bryl-Górecka, P.; Buch, S.; Buck, A.H.; Burger, D.; Busatto, S.; Buschmann, D.; Bussolati, B.; Buzás, E.I.; Byrd, J.B.; Camussi, G.; Carter, D.R.; Caruso, S.; Chamley, L.W.; Chang, Y.T.; Chen, C.; Chen, S.; Cheng, L.; Chin, A.R.; Clayton, A.; Clerici, S.P.; Cocks, A.; Cocucci, E.; Coffey, R.J.; Cordeiro-da-Silva, A.; Couch, Y.; Coumans, F.A.; Coyle, B.; Crescitelli, R.; Criado, M.F.; D’Souza-Schorey, C.; Das, S.; Datta Chaudhuri, A.; de Candia, P.; De Santana, E.F.; De Wever, O.; Del Portillo, H.A.; Demaret, T.; Deville, S.; Devitt, A.; Dhondt, B.; Di Vizio, D.; Dieterich, L.C.; Dolo, V.; Dominguez Rubio, A.P.; Dominici, M.; Dourado, M.R.; Driedonks, T.A.; Duarte, F.V.; Duncan, H.M.; Eichenberger, R.M.; Ekström, K.; El Andaloussi, S.; Elie-Caille, C.; Erdbrügger, U.; Falcón-Pérez, J.M.; Fatima, F.; Fish, J.E.; Flores-Bellver, M.; Försönits, A.; Frelet-Barrand, A.; Fricke, F.; Fuhrmann, G.; Gabrielsson, S.; Gámez-Valero, A.; Gardiner, C.; Gärtner, K.; Gaudin, R.; Gho, Y.S.; Giebel, B.; Gilbert, C.; Gimona, M.; Giusti, I.; Goberdhan, D.C.; Görgens, A.; Gorski, S.M.; Greening, D.W.; Gross, J.C.; Gualerzi, A.; Gupta, G.N.; Gustafson, D.; Handberg, A.; Haraszti, R.A.; Harrison, P.; Hegyesi, H.; Hendrix, A.; Hill, A.F.; Hochberg, F.H.; Hoffmann, K.F.; Holder, B.; Holthofer, H.; Hosseinkhani, B.; Hu, G.; Huang, Y.; Huber, V.; Hunt, S.; Ibrahim, A.G.; Ikezu, T.; Inal, J.M.; Isin, M.; Ivanova, A.; Jackson, H.K.; Jacobsen, S.; Jay, S.M.; Jayachandran, M.; Jenster, G.; Jiang, L.; Johnson, S.M.; Jones, J.C.; Jong, A.; Jovanovic-Talisman, T.; Jung, S.; Kalluri, R.; Kano, S.I.; Kaur, S.; Kawamura, Y.; Keller, E.T.; Khamari, D.; Khomyakova, E.; Khvorova, A.; Kierulf, P.; Kim, K.P.; Kislinger, T.; Klingeborn, M.; Klinke, D.J., II; Kornek, M.; Kosanović, M.M.; Kovács, Á.F.; Krämer-Albers, E.M.; Krasemann, S.; Krause, M.; Kurochkin, I.V.; Kusuma, G.D.; Kuypers, S.; Laitinen, S.; Langevin, S.M.; Languino, L.R.; Lannigan, J.; Lässer, C.; Laurent, L.C.; Lavieu, G.; Lázaro-Ibáñez, E.; Le Lay, S.; Lee, M.S.; Lee, Y.X.F.; Lemos, D.S.; Lenassi, M.; Leszczynska, A.; Li, I.T.; Liao, K.; Libregts, S.F.; Ligeti, E.; Lim, R.; Lim, S.K.; Linē, A.; Linnemannstöns, K.; Llorente, A.; Lombard, C.A.; Lorenowicz, M.J.; Lörincz, Á.M.; Lötvall, J.; Lovett, J.; Lowry, M.C.; Loyer, X.; Lu, Q.; Lukomska, B.; Lunavat, T.R.; Maas, S.L.; Malhi, H.; Marcilla, A.; Mariani, J.; Mariscal, J.; Martens-Uzunova, E.S.; Martin-Jaular, L.; Martinez, M.C.; Martins, V.R.; Mathieu, M.; Mathivanan, S.; Maugeri, M.; McGinnis, L.K.; McVey, M.J.; Meckes, D.G., Jr; Meehan, K.L.; Mertens, I.; Minciacchi, V.R.; Möller, A.; Møller Jørgensen, M.; Morales-Kastresana, A.; Morhayim, J.; Mullier, F.; Muraca, M.; Musante, L.; Mussack, V.; Muth, D.C.; Myburgh, K.H.; Najrana, T.; Nawaz, M.; Nazarenko, I.; Nejsum, P.; Neri, C.; Neri, T.; Nieuwland, R.; Nimrichter, L.; Nolan, J.P.; Nolte-’t Hoen, E.N.; Noren Hooten, N.; O’Driscoll, L.; O’Grady, T.; O’Loghlen, A.; Ochiya, T.; Olivier, M.; Ortiz, A.; Ortiz, L.A.; Osteikoetxea, X.; Østergaard, O.; Ostrowski, M.; Park, J.; Pegtel, D.M.; Peinado, H.; Perut, F.; Pfaffl, M.W.; Phinney, D.G.; Pieters, B.C.; Pink, R.C.; Pisetsky, D.S.; Pogge von Strandmann, E.; Polakovicova, I.; Poon, I.K.; Powell, B.H.; Prada, I.; Pulliam, L.; Quesenberry, P.; Radeghieri, A.; Raffai, R.L.; Raimondo, S.; Rak, J.; Ramirez, M.I.; Raposo, G.; Rayyan, M.S.; Regev-Rudzki, N.; Ricklefs, F.L.; Robbins, P.D.; Roberts, D.D.; Rodrigues, S.C.; Rohde, E.; Rome, S.; Rouschop, K.M.; Rughetti, A.; Russell, A.E.; Saá, P.; Sahoo, S.; Salas-Huenuleo, E.; Sánchez, C.; Saugstad, J.A.; Saul, M.J.; Schiffelers, R.M.; Schneider, R.; Schøyen, T.H.; Scott, A.; Shahaj, E.; Sharma, S.; Shatnyeva, O.; Shekari, F.; Shelke, G.V.; Shetty, A.K.; Shiba, K.; Siljander, P.R.; Silva, A.M.; Skowronek, A.; Snyder, O.L., II; Soares, R.P.; Sódar, B.W.; Soekmadji, C.; Sotillo, J.; Stahl, P.D.; Stoorvogel, W.; Stott, S.L.; Strasser, E.F.; Swift, S.; Tahara, H.; Tewari, M.; Timms, K.; Tiwari, S.; Tixeira, R.; Tkach, M.; Toh, W.S.; Tomasini, R.; Torrecilhas, A.C.; Tosar, J.P.; Toxavidis, V.; Urbanelli, L.; Vader, P.; van Balkom, B.W.; van der Grein, S.G.; Van Deun, J.; van Herwijnen, M.J.; Van Keuren-Jensen, K.; van Niel, G.; van Royen, M.E.; van Wijnen, A.J.; Vasconcelos, M.H.; Vechetti, I.J., Jr; Veit, T.D.; Vella, L.J.; Velot, É.; Verweij, F.J.; Vestad, B.; Viñas, J.L.; Visnovitz, T.; Vukman, K.V.; Wahlgren, J.; Watson, D.C.; Wauben, M.H.; Weaver, A.; Webber, J.P.; Weber, V.; Wehman, A.M.; Weiss, D.J.; Welsh, J.A.; Wendt, S.; Wheelock, A.M.; Wiener, Z.; Witte, L.; Wolfram, J.; Xagorari, A.; Xander, P.; Xu, J.; Yan, X.; Yáñez-Mó, M.; Yin, H.; Yuana, Y.; Zappulli, V.; Zarubova, J.; Žėkas, V.; Zhang, J.Y.; Zhao, Z.; Zheng, L.; Zheutlin, A.R.; Zickler, A.M.; Zimmermann, P.; Zivkovic, A.M.; Zocco, D.; Zuba-Surma, E.K. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles, 2018, 7(1), 1535750.
[http://dx.doi.org/10.1080/20013078.2018.1535750] [PMID: 30637094]
[81]
Witwer, K.W.; Théry, C. Extracellular vesicles or exosomes? On primacy, precision, and popularity influencing a choice of nomenclature. J. Extracell. Vesicles, 2019, 8(1), 1648167.
[http://dx.doi.org/10.1080/20013078.2019.1648167] [PMID: 31489144]
[82]
Elahi, F.M.; Farwell, D.G.; Nolta, J.A.; Anderson, J.D. Preclinical translation of exosomes derived from mesenchymal stem/stromal cells. Stem Cells, 2020, 38(1), 15-21.
[http://dx.doi.org/10.1002/stem.3061] [PMID: 31381842]
[83]
Hessvik, N.P.; Llorente, A. Current knowledge on exosome biogenesis and release. Cell. Mol. Life Sci., 2018, 75(2), 193-208.
[http://dx.doi.org/10.1007/s00018-017-2595-9] [PMID: 28733901]
[84]
Katsha, A.M.; Ohkouchi, S.; Xin, H.; Kanehira, M.; Sun, R.; Nukiwa, T.; Saijo, Y. Paracrine factors of multipotent stromal cells ameliorate lung injury in an elastase-induced emphysema model. Mol. Ther., 2011, 19(1), 196-203.
[http://dx.doi.org/10.1038/mt.2010.192] [PMID: 20842104]
[85]
Zhu, Y.G.; Feng, X.M.; Abbott, J.; Fang, X.H.; Hao, Q.; Monsel, A.; Qu, J.M.; Matthay, M.A.; Lee, J.W. Human mesenchymal stem cell microvesicles for treatment of Escherichia coli endotoxin-induced acute lung injury in mice. Stem Cells, 2014, 32(1), 116-125.
[http://dx.doi.org/10.1002/stem.1504] [PMID: 23939814]
[86]
Tang, X.D.; Shi, L.; Monsel, A.; Li, X.Y.; Zhu, H.L.; Zhu, Y.G.; Qu, J.M. Mesenchymal stem cell microvesicles attenuate acute lung injury in mice partly mediated by Ang‐1 mRNA. Stem Cells, 2017, 35(7), 1849-1859.
[http://dx.doi.org/10.1002/stem.2619] [PMID: 28376568]
[87]
Morrison, T.J.; Jackson, M.V.; Cunningham, E.K.; Kissenpfennig, A.; McAuley, D.F.; O’Kane, C.M.; Krasnodembskaya, A.D. Mesenchymal stromal cells modulate macrophages in clinically relevant lung injury models by extracellular vesicle mitochondrial transfer. Am. J. Respir. Crit. Care Med., 2017, 196(10), 1275-1286.
[http://dx.doi.org/10.1164/rccm.201701-0170OC] [PMID: 28598224]
[88]
Wang, M.; Yuan, Q.; Xie, L. Mesenchymal stem cell-based immunomodulation: properties and clinical application. Stem Cells Int., 2018, 2018, 3057624.
[http://dx.doi.org/10.1155/2018/3057624]


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VOLUME: 28
ISSUE: 8
Year: 2021
Published on: 22 February, 2021
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DOI: 10.2174/0929866528666210222150347
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