Download PDF
CC BY-NC-ND 4.0 · Ann Natl Acad Med Sci 2021; 57(04): 202-213
DOI: 10.1055/s-0041-1731597
Review Article

A Step Toward Optimizing Regenerative Medicine Principle to Combat COVID-19

Shilpa Sharma 
1   Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
,
Madhan Jeyaraman 
2   Department of Orthopaedics, School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
,
Sathish Muthu 
3   Department of Orthopaedics, Government Medical College and Hospital, Dindigul, Tamil Nadu, India
,
Talagavadi Channaiah Anudeep 
4   Department of Plastic Surgery, Topiwala National Medical College and BYL Nair Ch. Hospital, Mumbai, Maharashtra, India
,
Naveen Jeyaraman 
5   Department of Orthopaedics, Kasturba Medical College, MAHE University, Manipal, Karnataka, India
,
Ajay Satish Shringeri 
6   Department of Orthopedics, Sri Devaraj URS Medical College, Kolar, Karnataka, India
,
Vinodh Kumar 
7   Biocon Biologics, Chennai, Tamil Nadu, India
,
Rajeswari Somasundaram 
8   Department of Microbiology, PSG BioNEST, PSG TECH, Coimbatore, Tamil Nadu, India
,
Rashmi Jain 
9   School of Medical Sciences and Research, Sharda University, Greater Noida, Uttar Pradesh, India
,
Saurabh Kumar Jha 
10   Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida, Uttar Pradesh, India
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

Drugs are currently not licensed in specific to pulverize COVID-19. On an emergency basis, vaccines were approved to prevent the further spread of COVID-19. This serves as a potential background for considering the optimization of biologics. In this context, evidence on convalescent plasma and stem cells has shown a beneficial role. Here, we have considered this as plausible therapy, and further hypothesize that their cocktails will synergistically boost the immunogenicity to relegate COVID-19. This warrants a large volume clinical trial on an emergent basis, because the sooner we establish a safe and effective cure, the better.

Keywords

COVID-19 - mesenchymal stem cells - convalescent plasma - pandemic


Publication History

Article published online:
21 June 2021

© 2021. National Academy of Medical Sciences (India). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Coronavirus Disease (COVID-19) Situation Reports. Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports. Accessed March 8, 2021
  • 2 Abd El-Aziz TM, Stockand JD. Recent progress and challenges in drug development against COVID-19 coronavirus (SARS-CoV-2) - an update on the status. Infect Genet Evol 2020; 83: 104327
    CrossrefPubMedGoogle Scholar
  • 3 McKee DL, Sternberg A, Stange U, Laufer S, Naujokat C. Candidate drugs against SARS-CoV-2 and COVID-19. Pharmacol Res 2020; 157: 104859
    CrossrefPubMedGoogle Scholar
  • 4 “Solidarity” clinical trial for COVID-19 treatments. Available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov/solidarity-clinical-trial-for-covid-19-treatments. Accessed March 8, 2021
  • 5 Uzunova K, Filipova E, Pavlova V, Vekov T. Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. Biomed Pharmacother 2020; 131: 110668
    CrossrefPubMedGoogle Scholar
  • 6 Tobaiqy M, Qashqary M, Al-Dahery S. et al Therapeutic management of patients with COVID-19: a systematic review. Infect Prev Pract 2020; 2 (03) 100061
    CrossrefPubMedGoogle Scholar
  • 7 Thiagarajan K. Covid-19: India is at centre of global vaccine manufacturing, but opacity threatens public trust. BMJ 2021; 372 (196) n196
    CrossrefPubMedGoogle Scholar
  • 8 Li L, Zhang W, Hu Y. et al Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19: a randomized clinical trial. JAMA 2020; 324 (05) 460-470
    CrossrefPubMedGoogle Scholar
  • 9 Chen L, Xiong J, Bao L, Shi Y. Convalescent plasma as a potential therapy for COVID-19. Lancet Infect Dis 2020; 20 (04) 398-400
    CrossrefPubMedGoogle Scholar
  • 10 Abolghasemi H, Eshghi P, Cheraghali AM. et al Clinical efficacy of convalescent plasma for treatment of COVID-19 infections: Results of a multicenter clinical study. Transfus Apheresis Sci 2020; 59 (05) 102875
    CrossrefPubMedGoogle Scholar
  • 11 Klasse PJ. Neutralization of virus infectivity by antibodies: old problems in new perspectives. Adv Biol 2014; 2014: 157895
    CrossrefPubMedGoogle Scholar
  • 12 Coughlin MM, Prabhakar BS. Neutralizing human monoclonal antibodies to severe acute respiratory syndrome coronavirus: target, mechanism of action, and therapeutic potential. Rev Med Virol 2012; 22 (01) 2-17
    CrossrefPubMedGoogle Scholar
  • 13 Marano G, Vaglio S, Pupella S. et al Convalescent plasma: new evidence for an old therapeutic tool?. Blood Transfus 2016; 14 (02) 152-157
    PubMedGoogle Scholar
  • 14 Zhao Q, He Y. Challenges of convalescent plasma therapy on COVID-19. J Clin Virol 2020; 127: 104358
    CrossrefPubMedGoogle Scholar
  • 15 Rojas M, Rodríguez Y, Monsalve DM. et al Convalescent plasma in Covid-19: Possible mechanisms of action. Autoimmun Rev 2020; 19 (07) 102554
    CrossrefPubMedGoogle Scholar
  • 16 Shamim S, Khan M, Kharaba ZJ, Ijaz M, Murtaza G. Potential strategies for combating COVID-19. Arch Virol 2020; 165 (11) 2419-2438
    CrossrefPubMedGoogle Scholar
  • 17 Piyush R, Rajarshi K, Khan R, Ray S. Convalescent plasma therapy: a promising coronavirus disease 2019 treatment strategy. Open Biol 2020; 10 (09) 200174
    CrossrefPubMedGoogle Scholar
  • 18 Wooding DJ, Bach H. Treatment of COVID-19 with convalescent plasma: lessons from past coronavirus outbreaks. Clin Microbiol Infect 2020; 26 (10) 1436-1446
    CrossrefPubMedGoogle Scholar
  • 19 Liu L, Wei Q, Lin Q. et al Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection. JCI Insight 2019; 4 (04) 123158
    CrossrefPubMedGoogle Scholar
  • 20 Iqbal H. The importance of cell-mediated immunity in COVID-19 - An opinion. Med Hypotheses 2020; 143: 110152
    CrossrefPubMedGoogle Scholar
  • 21 Selvi V. Convalescent plasma: a challenging tool to treat COVID-19 Patients-A lesson from the past and new perspectives. BioMed Res Int 2020; 2020: 2606058
    CrossrefPubMedGoogle Scholar
  • 22 Wong VWS, Dai D, Wu AKL, Sung JJ. Treatment of severe acute respiratory syndrome with convalescent plasma. Hong Kong Med J 2003; 9 (03) 199-201
    PubMedGoogle Scholar
  • 23 Şimşek Yavuz S, Ünal S. Antiviral treatment of COVID-19. Turk J Med Sci 2020; 50 (SI-1) 611-619
    CrossrefPubMedGoogle Scholar
  • 24 Poutanen SM, Low DE, Henry B. et al National Microbiology Laboratory, Canada; Canadian Severe Acute Respiratory Syndrome Study Team. Identification of severe acute respiratory syndrome in Canada. N Engl J Med 2003; 348 (20) 1995-2005
    CrossrefPubMedGoogle Scholar
  • 25 The PREVENT Study Group. Reduction of respiratory syncytial virus hospitalization among premature infants and infants with bronchopulmonary dysplasia using respiratory syncytial virus immune globulin prophylaxis. Pediatrics 1997; 99 (01) 93-99
    CrossrefPubMedGoogle Scholar
  • 26 Leider JP, Brunker PAR, Ness PM. Convalescent transfusion for pandemic influenza: preparing blood banks for a new plasma product?. Transfusion 2010; 50 (06) 1384-1398
    CrossrefPubMedGoogle Scholar
  • 27 Rosenke K, Bounds CE, Hanley PW. et al Human polyclonal antibodies produced by transchromosomal cattle provide partial protection against lethal Zaire Ebolavirus challenge in Rhesus macaques. J Infect Dis 2018; 218 (suppl_5) S658-S661
    CrossrefPubMedGoogle Scholar
  • 28 Duan K, Liu B, Li C. et al Effectiveness of convalescent plasma therapy in severe COVID-19 patients. Proc Natl Acad Sci U S A 2020; 117 (17) 9490-9496
    CrossrefPubMedGoogle Scholar
  • 29 Verma HK, Farran B, Bhaskar LVKS. Convalescent plasma transfusion a promising therapy for coronavirus diseases 2019 (COVID-19): current updates. Antib Ther 2020; 3 (02) 115-125
    PubMedGoogle Scholar
  • 30 Christ GJ, Saul JM, Furth ME, Andersson K-E. The pharmacology of regenerative medicine. Pharmacol Rev 2013; 65 (03) 1091-1133
    CrossrefPubMedGoogle Scholar
  • 31 Dzobo K, Thomford NE, Senthebane DA. et al Advances in regenerative medicine and tissue engineering: innovation and transformation of medicine. Stem Cells Int 2018; 2018: 2495848
    CrossrefPubMedGoogle Scholar
  • 32 Chen F-M, Liu X. Advancing biomaterials of human origin for tissue engineering. Prog Polym Sci 2016; 53: 86-168
    CrossrefPubMedGoogle Scholar
  • 33 Christ B, Franquesa M, Najimi M, van der Laan LJW, Dahlke MH. Cellular and molecular mechanisms of mesenchymal stem cell actions. Stem Cells Int 2017; 2017: 2489041
    CrossrefPubMedGoogle Scholar
  • 34 Foley L, Whitaker M. Concise review: cell therapies: the route to widespread adoption. Stem Cells Transl Med 2012; 1 (05) 438-447
    CrossrefPubMedGoogle Scholar
  • 35 Abdelrazik H, Giordano E, Barbanti Brodano G, Griffoni C, De Falco E, Pelagalli A. Substantial overview on mesenchymal stem cell biological and physical properties as an opportunity in translational medicine. Int J Mol Sci 2019; 20 (21) E5386
    CrossrefPubMedGoogle Scholar
  • 36 Han Y, Li X, Zhang Y, Han Y, Chang F, Ding J. Mesenchymal stem cells for regenerative medicine. Cells 2019; 8 (08) E886
    CrossrefPubMedGoogle Scholar
  • 37 Green EM, Lee RT. Proteins and small molecules for cellular regenerative medicine. Physiol Rev 2013; 93 (01) 311-325
    CrossrefPubMedGoogle Scholar
  • 38 Biehl JK, Russell B. Introduction to stem cell therapy. J Cardiovasc Nurs 2009; 24 (02) 98-103 quiz 104–105
    CrossrefPubMedGoogle Scholar
  • 39 Okano H, Sipp D. New trends in cellular therapy. Development 2020; 147 (18) dev192567
    CrossrefPubMedGoogle Scholar
  • 40 Jeyaraman M, Ranjan R, Kumar R. et al Cellular therapy: shafts of light emerging for COVID-19. Stem Cell Investig 2020; 7: 11
    CrossrefPubMedGoogle Scholar
  • 41 Jeyaraman M, John A, Koshy S. et al Fostering mesenchymal stem cell therapy to halt cytokine storm in COVID-19. Biochim Biophys Acta Mol Basis Dis 2021; 1867 (02) 166014
    CrossrefPubMedGoogle Scholar
  • 42 Yorukoglu AC, Kiter AE, Akkaya S, Satiroglu-Tufan NL, Tufan AC. A concise review on the use of mesenchymal stem cells in cell sheet-based tissue engineering with special emphasis on bone tissue regeneration. Stem Cells Int 2017; 2017: 2374161
    CrossrefPubMedGoogle Scholar
  • 43 Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep 2015; 35 (02) e00191
    CrossrefPubMedGoogle Scholar
  • 44 Volarevic V, Markovic BS, Gazdic M. et al Ethical and safety issues of stem cell-based therapy. Int J Med Sci 2018; 15 (01) 36-45
    CrossrefPubMedGoogle Scholar
  • 45 Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med 2019; 4 (01) 22
    CrossrefPubMedGoogle Scholar
  • 46 Wei X, Yang X, Han ZP, Qu FF, Shao L, Shi YF. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin 2013; 34 (06) 747-754
    CrossrefPubMedGoogle Scholar
  • 47 Berebichez-Fridman R, Montero-Olvera PR. Sources and clinical applications of mesenchymal stem cells: state-of-the-art review. Sultan Qaboos Univ Med J 2018; 18 (03) e264-e277
    CrossrefPubMedGoogle Scholar
  • 48 Kangari P, Talaei-Khozani T, Razeghian-Jahromi I, Razmkhah M. Mesenchymal stem cells: amazing remedies for bone and cartilage defects. Stem Cell Res Ther 2020; 11 (01) 49
    CrossrefPubMedGoogle Scholar
  • 49 Paul D, Samuel SM, Maulik N. Mesenchymal stem cell: present challenges and prospective cellular cardiomyoplasty approaches for myocardial regeneration. Antioxid Redox Signal 2009; 11 (08) 1841-1855
    CrossrefPubMedGoogle Scholar
  • 50 Gianakos AL, Sun L, Patel JN, Adams DM, Liporace FA. Clinical application of concentrated bone marrow aspirate in orthopaedics: A systematic review. World J Orthop 2017; 8 (06) 491-506
    CrossrefPubMedGoogle Scholar
  • 51 Zhao Q, Ren H, Han Z. Mesenchymal stem cells: immunomodulatory capability and clinical potential in immune diseases. J Cell Immunother 2016; 2 (01) 3-20
    CrossrefGoogle Scholar
  • 52 Bora P, Majumdar AS. Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation. Stem Cell Res Ther 2017; 8 (01) 145
    CrossrefPubMedGoogle Scholar
  • 53 Gentile P, Scioli MG, Bielli A, Orlandi A, Cervelli V. Comparing different nanofat procedures on scars: role of the stromal vascular fraction and its clinical implications. Regen Med 2017; 12 (08) 939-952
    CrossrefPubMedGoogle Scholar
  • 54 Alexander RW. Understanding adipose-derived stromal vascular fraction (AD-SVF) cell biology and use on the basis of cellular, chemical, structural and paracrine components: a concise review. Journal of Prolotherapy 2012; 4: e855-e869
    Google Scholar
  • 55 Mazini L, Rochette L, Amine M, Malka G. Regenerative capacity of adipose derived stem cells (ADSCs), comparison with mesenchymal stem cells (MSCs). Int J Mol Sci 2019; 20 (10) E2523
    CrossrefPubMedGoogle Scholar
  • 56 Chu D-T, Nguyen Thi Phuong T, Tien NLB. et al Adipose tissue stem cells for therapy: an update on the progress of isolation, culture, storage, and clinical application. J Clin Med 2019; 8 (07) E917
    CrossrefPubMedGoogle Scholar
  • 57 Atluri S, Manchikanti L, Hirsch JA. Expanded umbilical cord mesenchymal stem cells (UC-MSCs) as a therapeutic strategy in managing critically ill COVID-19 patients: the case for compassionate use. Pain Physician 2020; 23 (02) E71-E83
    PubMedGoogle Scholar
  • 58 Marmotti A, Mattia S, Castoldi F. et al Allogeneic umbilical cord-derived mesenchymal stem cells as a potential source for cartilage and bone regeneration: an in vitro study. Stem Cells Int 2017; 2017: 1732094
    CrossrefPubMedGoogle Scholar
  • 59 Rady D, Abbass MM, El-Rashidy AA. et al Mesenchymal stem/progenitor cells: the prospect of human clinical translation. Stem Cells Int 2020; 2020: 8837654
    CrossrefPubMedGoogle Scholar
  • 60 Parekkadan B, Milwid JM. Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng 2010; 12: 87-117
    CrossrefPubMedGoogle Scholar
  • 61 Weiss ARR, Dahlke MH. Immunomodulation by mesenchymal stem cells (MSCs): mechanisms of action of living, apoptotic, and dead MSCs. Front Immunol 2019; 10: 1191
    CrossrefPubMedGoogle Scholar
  • 62 Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH. Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes 2008; 57 (07) 1759-1767
    CrossrefPubMedGoogle Scholar
  • 63 Kyurkchiev D, Bochev I, Ivanova-Todorova E. et al Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells 2014; 6 (05) 552-570
    CrossrefPubMedGoogle Scholar
  • 64 Machado Cde V, Telles PD, Nascimento IL. Immunological characteristics of mesenchymal stem cells. Rev Bras Hematol Hemoter 2013; 35 (01) 62-67
    CrossrefPubMedGoogle Scholar
  • 65 Lee JW, Fang X, Krasnodembskaya A, Howard JP, Matthay MA. Concise review: Mesenchymal stem cells for acute lung injury: role of paracrine soluble factors. Stem Cells 2011; 29 (06) 913-919
    CrossrefPubMedGoogle Scholar
  • 66 Lu Z, Chang W, Meng S. et al Mesenchymal stem cells induce dendritic cell immune tolerance via paracrine hepatocyte growth factor to alleviate acute lung injury. Stem Cell Res Ther 2019; 10 (01) 372
    CrossrefPubMedGoogle Scholar
  • 67 Alcayaga-Miranda F, Cuenca J, Khoury M. Antimicrobial activity of mesenchymal stem cells: current status and new perspectives of antimicrobial peptide-based therapies. Front Immunol 2017; 8: 339
    CrossrefPubMedGoogle Scholar
  • 68 Yagi H, Chen AF, Hirsch D. et al Antimicrobial activity of mesenchymal stem cells against Staphylococcus aureus. Stem Cell Res Ther 2020; 11 (01) 293
    CrossrefPubMedGoogle Scholar
  • 69 Sutton MT, Fletcher D, Ghosh SK. et al Antimicrobial properties of mesenchymal stem cells: therapeutic potential for cystic fibrosis infection, and treatment. Stem Cells Int 2016; 2016: 5303048
    CrossrefPubMedGoogle Scholar
  • 70 Shah VK, Firmal P, Alam A, Ganguly D, Chattopadhyay S. Overview of immune response during SARS-CoV-2 Infection: lessons from the past. Front Immunol 2020; 11: 1949
    CrossrefPubMedGoogle Scholar
  • 71 Crivelli B, Chlapanidas T, Perteghella S. et al Italian Mesenchymal Stem Cell Group (GISM). Mesenchymal stem/stromal cell extracellular vesicles: from active principle to next generation drug delivery system. J Control Release 2017; 262: 104-117
    CrossrefPubMedGoogle Scholar
  • 72 Gupta A, Kashte S, Gupta M, Rodriguez HC, Gautam SS, Kadam S. Mesenchymal stem cells and exosome therapy for COVID-19: current status and future perspective. Hum Cell 2020; 33 (04) 907-918
    CrossrefPubMedGoogle Scholar
  • 73 Rezakhani L, Kelishadrokhi AF, Soleimanizadeh A, Rahmati S. Mesenchymal stem cell (MSC)-derived exosomes as a cell-free therapy for patients infected with COVID-19: real opportunities and range of promises. Chem Phys Lipids 2021; 234: 105009
    CrossrefPubMedGoogle Scholar
  • 74 Pinky GuptaS, Krishnakumar V, Sharma Y, Dinda AK, Mohanty S. Mesenchymal stem cell derived exosomes: a nano platform for therapeutics and drug delivery in combating COVID-19. Stem Cell Rev Rep 2021; 17 (01) 33-43
    CrossrefPubMedGoogle Scholar
  • 75 Zhou P, Yang X-L, Wang X-G. et al A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020; 579 (7798) 270-273
    CrossrefPubMedGoogle Scholar
  • 76 Grein J, Ohmagari N, Shin D. et al Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med 2020; 382 (24) 2327-2336
    CrossrefPubMedGoogle Scholar
  • 77 Ma N, Gai H, Mei J. et al Bone marrow mesenchymal stem cells can differentiate into type II alveolar epithelial cells in vitro. Cell Biol Int 2011; 35 (12) 1261-1266
    CrossrefPubMedGoogle Scholar
  • 78 Lanzoni G, Linetsky E, Correa D. et al Umbilical cord mesenchymal stem cells for COVID-19 acute respiratory distress syndrome: A double-blind, phase 1/2a, randomized controlled trial. Stem Cells Transl Med 2021; 10 (05) 660-673
    CrossrefPubMedGoogle Scholar
  • 79 Tzouvelekis A, Paspaliaris V, Koliakos G. et al A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to study the safety of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis. J Transl Med 2013; 11: 171
    CrossrefPubMedGoogle Scholar
  • 80 Cardenes N, Aranda-Valderrama P, Carney JP. et al Cell therapy for ARDS: efficacy of endobronchial versus intravenous administration and biodistribution of MAPCs in a large animal model. BMJ Open Respir Res 2019; 6 (01) e000308
    CrossrefPubMedGoogle Scholar
  • 81 Antoniou KM, Karagiannis K, Tsitoura E. et al Clinical applications of mesenchymal stem cells in chronic lung diseases. Biomed Rep 2018; 8 (04) 314-318
    PubMedGoogle Scholar
  • 82 Cheng S-L, Lin C-H, Yao C-L. Mesenchymal stem cell administration in patients with chronic obstructive pulmonary disease: state of the science. Stem Cells Int 2017; 2017: 8916570
    PubMedGoogle Scholar
  • 83 Hoffmann M, Kleine-Weber H, Schroeder S. et al SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell 2020; 181 (02) 271-280.e8
    CrossrefPubMedGoogle Scholar
  • 84 Wruck W, Adjaye J. SARS-CoV-2 receptor ACE2 is co-expressed with genes related to transmembrane serine proteases, viral entry, immunity and cellular stress. Sci Rep 2020; 10 (01) 21415
    CrossrefPubMedGoogle Scholar
  • 85 Hamming I, Timens W, Bulthuis MLC. Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol 2004; 203 (02) 631-637
    CrossrefPubMedGoogle Scholar
  • 86 Song P, Li W, Xie J, Hou Y, You C. Cytokine storm induced by SARS-CoV-2. Clin Chim Acta 2020; 509: 280-287
    CrossrefPubMedGoogle Scholar
  • 87 Al-Khawaga S, Abdelalim EM. Potential application of mesenchymal stem cells and their exosomes in lung injury: an emerging therapeutic option for COVID-19 patients. Stem Cell Res Ther 2020; 11 (01) 437
    CrossrefPubMedGoogle Scholar
  • 88 Durand N, Mallea J, Zubair AC. Insights into the use of mesenchymal stem cells in COVID-19 mediated acute respiratory failure. NPJ Regen Med 2020; 5 (01) 17
    CrossrefPubMedGoogle Scholar
  • 89 Raza SS, Khan MA. Mesenchymal stem cells: A new front emerge in COVID19 treatment. Cytotherapy 2020; Doi: DOI: 10.1016/j.jcyt.2020.07.002.
    CrossrefPubMedGoogle Scholar
  • 90 Advanced Search - ClinicalTrials.gov. Available at: https://clinicaltrials.gov/ct2/search/advanced. Accessed March 9, 2021
  • 91 Leng Z, Zhu R, Hou W. et al Transplantation of ACE2- mesenchymal stem cells improves the outcome of patients with COVID-19 pneumonia. Aging Dis 2020; 11 (02) 216-228
    CrossrefPubMedGoogle Scholar
  • 92 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. Medicine (Baltimore) 2020; 99 (31) e21429
    CrossrefPubMedGoogle Scholar
  • 93 Lukomska B, Stanaszek L, Zuba-Surma E, Legosz P, Sarzynska S, Drela K. Challenges and controversies in human mesenchymal stem cell therapy. Stem Cells Int 2019; 2019: 9628536
    CrossrefPubMedGoogle Scholar
  • 94 Ikebe C, Suzuki K. Mesenchymal stem cells for regenerative therapy: optimization of cell preparation protocols. BioMed Res Int 2014; 2014: 951512
    CrossrefPubMedGoogle Scholar
  • 95 Torre ML, Lucarelli E, Guidi S. et al Gruppo Italiano Staminali Mesenchimali (GISM). Ex vivo expanded mesenchymal stromal cell minimal quality requirements for clinical application. Stem Cells Dev 2015; 24 (06) 677-685
    CrossrefPubMedGoogle Scholar
  • 96 Codinach M, Blanco M, Ortega I. et al Design and validation of a consistent and reproducible manufacture process for the production of clinical-grade bone marrow-derived multipotent mesenchymal stromal cells. Cytotherapy 2016; 18 (09) 1197-1208
    CrossrefPubMedGoogle Scholar
  • 97 Grisendi G, Annerén C, Cafarelli L. et al GMP-manufactured density gradient media for optimized mesenchymal stromal/stem cell isolation and expansion. Cytotherapy 2010; 12 (04) 466-477
    CrossrefPubMedGoogle Scholar
  • 98 Wuchter P, Bieback K, Schrezenmeier H. et al Standardization of Good Manufacturing Practice-compliant production of bone marrow-derived human mesenchymal stromal cells for immunotherapeutic applications. Cytotherapy 2015; 17 (02) 128-139
    CrossrefPubMedGoogle Scholar
  • 99 Deasy BM, Anderson JE, Zelina S. Regulatory issues in the therapeutic use of stem cells. Regen Med Tissue Eng 2013; Doi: DOI: 10.5772/55945.
    CrossrefGoogle Scholar
  • 100 Peng H, Gong T, Huang X. et al A synergistic role of convalescent plasma and mesenchymal stem cells in the treatment of severely ill COVID-19 patients: a clinical case report. Stem Cell Res Ther 2020; 11 (01) 291
    CrossrefPubMedGoogle Scholar
  • 101 Kavianpour M, Saleh M, Verdi J. The role of mesenchymal stromal cells in immune modulation of COVID-19: focus on cytokine storm. Stem Cell Res Ther 2020; 11 (01) 404
    CrossrefPubMedGoogle Scholar
  • 102 Fan X-L, Zhang Y, Li X, Fu Q-L. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci 2020; 77 (14) 2771-2794
    CrossrefPubMedGoogle Scholar
  • 103 Naji A, Favier B, Deschaseaux F, Rouas-Freiss N, Eitoku M, Suganuma N. Mesenchymal stem/stromal cell function in modulating cell death. Stem Cell Res Ther 2019; 10 (01) 56
    CrossrefPubMedGoogle Scholar
  • 104 Weiss DJ, English K, Krasnodembskaya A, Isaza-Correa JM, Hawthorne IJ, Mahon BP. The necrobiology of mesenchymal stromal cells affects therapeutic efficacy. Front Immunol 2019; 10: 1228
    CrossrefPubMedGoogle Scholar
  • 105 Robbins JB, Schneerson R, Szu SC. Perspective: hypothesis: serum IgG antibody is sufficient to confer protection against infectious diseases by inactivating the inoculum. J Infect Dis 1995; 171 (06) 1387-1398
    CrossrefPubMedGoogle Scholar
  • 106 Casadevall A, Pirofski LA. Antibody-mediated regulation of cellular immunity and the inflammatory response. Trends Immunol 2003; 24 (09) 474-478
    CrossrefPubMedGoogle Scholar
  • 107 Casadevall A, Scharff MD. Serum therapy revisited: animal models of infection and development of passive antibody therapy. Antimicrob Agents Chemother 1994; 38 (08) 1695-1702
    CrossrefPubMedGoogle Scholar