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COVID-19 Embryonic Stem Cell Transplanta - tion Zuangrong Sheepsattayakorn Department of Pathology, Faculty of Medicine, Chiang Mai Universi- ty, Chiang Mai, Thailand *Corresponding Author : Zuangrong Sheepsattayakorn, Department of Pathology, Faculty of Medicine, Chiang Mai Uni- versity, Chiang Mai, Thailand Received : August 18, 2023 ; Accepted : August 19, 2023 ; Published : September 21, 2023 ; Editorial Mesenchymal stem cell (MSC) populations that possess compa- rable potential for multi-lineage differentiation have been iso- lated in vitro from a variety of bone marrow (BM) and non-BM tissues, such as the placenta, adipose tissue, amniotic fluid, um- bilical cord, and peripheral blood [1–10]. Ten to one hundred Colony-Forming Unit-Fibroblast (CFU-F) per 106 Marrow Mono- nuclear Cells (MNCs) make up the clonogenic BM-human MSC fraction [11]. Human leukocyte antigen (HLA)-DR expression, multipotency (i.e., chondrogenic, osteogenic, and adipogenic), positive expression of surface antigens CD73, CD90, and CD105, and adherence to plastic are the characteristics of BM-human MCSs [11]. By 2000, physicians’ interest in intravenously admin- istered MSC treatment had grown [12]. A prior work showed that both human and murine MCSs can cause immunological suppression by drawing in and eliminating auto-reactive T cells through FasL, which in turn promotes macrophage production of TGF-β and the development of regulatory T cells [13]. The connection between MSC-induced Monocyte Chemoattractant Protein-1 (MCP-1) secretion and dying T cells triggers macro- phages to release TGF-β, which in turn activates regulatory T cells and enhances immunological tolerance [14]. The thera- peutic importance of MSCs was emphasised by their ability to promote wound healing and differentiate and engraft in vivo [15–21]. The recommendations for MSC characterization were devel- oped in 2006 by the International Society for Cellular Therapy. They aim to standardise information regarding the biology, definition, isolation, and characterization criteria of MSCs, their significance in vivo, and institutional and ethical laws related to their clinical usage [11]. Several studies have been studied in China since the COVID-19 pandemic. For example, the follow- ing ClinicalYtrials.gov identifiers are being used to fight against severe COVID-19 or COVID-19 pneumonia: NCT04252118, NCT04273646, NCT04276987, NCT04293692, NCT04302519, NCT04288102, etc. [22–27]. MSCs can help regulate the immune system and help patients return to normal, especially the elder- ly [28]. They can also reduce the overabundance of inflammato- ry chemicals and the overproduction of immune cells brought on by the COVID-19 [28]. In conclusion, clinical investigations have shown that human MSCs are safe and are presently being considered as a stem cell treatment for several disorders, including severe COVID-19. However, more research is urgently required to examine and refine several aspects of the human MSC culture environment through the creation of a bioprocess that can be run in compli- ance with Good Manufacturing Practises (GMP). References 1. Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Cir Res 2011; 109 (8): 923- 940. 2. Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH. Iso- lation of multipotent mesenchymal stem cells from umbil- ical cord blood. Blood 2004; 103 (5): 1669-1675. 3. Wang HS, Hung CS, Peng ST, Huang CC, Wei HM, Guo YJ, et al. Mesenchymal stem cells in the Wharton’s jelly of the human umbilical cord. Stem Cells 2004; 22 (7): 1330-1337. 4. Tondreau T, Meuleman N, Delforge A, Dejeneffe M, Leroy R, Massy M, et al. Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood : proliferation, Oct4 expression, and plasticity. Stem Cells 2005; 23 (8): 1105-1112. www.directivepublications.org Page - 1 The Journal of Clinical Microbiology Editorial
5. Vellasamy S, Sandrasaigaran P, Vidyadaran S, George E, Ramasamy R. Isolation and characterization of mesenchy- mal stem cells derived from human placenta tissue. World J Stem Cells 2012; 4 (6): 53-61. 6. Anker PS l’t, Scherjon SA, Kleijburg-van der Keur C, Noort WA, Claas FH, Willemze R, et al. Amniotic fluid as a novel source of mesenchymal stem cells for therapeutic trans- plantation. Blood 2003; 102 (4): 1548-1549. 7. De Coppi P, Bartsch Jr G, Siddiqui MM, Xu T, Santos CC, Perin, et al. Isolation of amniotic stem cell lines with po- tential for therapy. Nat Biotechnol 2007; 25 (1): 100-106. 8. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 2002; 13 (12): 4279-4295. 9. Gimble J, Guilak F. Adipose-derived adult stem cells: isola- tion, characterization, and differentiation potential. Cyto- therapy 2003; 5 (5): 362-369. 10. Zvaifler NJ, Marinova-Mutafchieva L, Adams G, Edwards CJ, Moss J, Burger JA, et al. Mesenchymal precursor cells in the blood of normal individuals. Arthritis Res 2000; 2 (6): 477-488. 11. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining mul- tipotent mesenchymal stromal cells, the International So- ciety for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-317. 12. Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, et al. Isolated allogeneic bone marrow-derived mes- enchymal cells engraft for cell therapy of bone. Proc Natl Acad Sci 2002; 99: 8932-8937. 13. Akiyama K, Chen C, Wang D, Xu X, Qu C, Yamaza T, et al. Mesenchymal stem cell-induced immunoregulation in- volves Fas ligand/Fas-mediated T cell apoptosis. Cell Stem Cell 2012; 10 (5): 544-555. 14. Choi H, Lee RH, Bazhanov N, Oh JY, Prockop DJ. Anti-in- flammatory protein TSG-6 secreted by activated MSCs at- tenuates zymosan-induced mouse peritonitis by decreas- ing TLR2/NF-Kb signaling in resident macrophages. Blood 2011; 118: 330-338. 15. Karp JM, Leng Teo GS. Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 2009; 4 (3): 206-216. 16. Sivanathan KN, Gronthos S, Rojas-Canales D, Thierry B, Coates PT. Interferon-gamma modification of mesenchy- mal stem cells : implications of autologous and allogene- ic mesenchymal stem cell therapy in allotransplantation. Stem Cell Rev 2014; 10 (3): 351-375. 17. Nemeth K, Keane-Myers A, Brown JM, Metcalfe DD, Gor- ham JD, Bundoc VG, et al. Bone marrow stromal cells use TGF-beta to suppress allergic responses in a mouse mod- el of ragweed-induced asthma. Proc Natl Acad Sci 2010; 107 (12): 5652-5657. 18. Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric ox- ide. Cell Stem Cell 2008; 2 (2): 141-150. 19. English K, French A, Wood KJ. Mesenchymal stromal cells: facilitators of successful transplantation? Cell Stem Cell 2010; 7 (4): 431-442. 20. Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regen- erative medicine. Exp Mol Med 2013; 45: e54. 21. Tyndall A. Mesenchymal stem cell treatments in rheuma- tology: a glass half full? Nat Rev Rheumatol 2014; 10 (2): 117-124. 22. Beijing 302 Hospital, China. ClinicalTrials.gov Identifi- er: NCT04252118. Mesenchymal stem cell treatment for pneumonia patients infected with 2019 novel coro- navirus. Available at: https://clinicaltrials.gov/ct2/show/ NCT04252118?show_xprt=Y (accessed on March 28, 2020). 23. Wuhan Union Hospital, China. ClinicalTrials.gov Identi- fier: NCT04273646. Study of human umbilical cord mes- enchymal stem cells in the treatment of novel coronavi- rus severe pneumonia. Available at: https://clinicaltrials. gov/ct2/show/NCT04273646?show_xcprt=Y (accessed on March 28, 2020). www.directivepublications.org Page - 2 The Journal of Clinical Microbiology Editorial
24. Ruijin Hospital, China. ClinicalTrials.gov Identifier: NCT04276987. A pilot clinical study on inhalation of mes- enchymal stem cells exosomes treating severe novel coronavirus pneumonia. Available at:https://clinicaltrials. gov/ct2/show/NCT04276987?show_xprt=Y (accessed on March 28, 2020). 25. Puren Hospital Affiliated to Wuhan University of Sci- ence and Technology, China. ClinicalTrilas.gov Identifier: NCT04293692. Therapy for pneumonia patients infected by 2019 novel coronavirus. Available at: https://clinicaltri- als.gov/ct2/show/NCT04293692?show_xprt=Y (accessed on March 28, 2020). 26. CAR-T (Shanghai) Biotechnology Co., Ltd., China. Clinical- Trials.gov Identifier: NCT04302519. Novel coronavirus induced severe pneumonia treated by dental pulp mes- enchymal stem cells. Available at: https://clinicaltrials. gov/ct2/show/NCT04302519?show_xprt=Y (accessed on March 28, 2020). 27. Beijing 302 Hospital, China. ClinicalTrials.gov Identifier: NCT04288102. Treatment with mesenchymal stem cells for severe coronavirus disease 2019 (COVID-19). Available at: https://clinicaltrials.gov/ct2/show/NCT04288102 (ac- cessed on March 28, 2020). 28. Liying Z. China.org.cn. Mesenchymal stem cell thera- py shows promise in treating COVID-19. Published on- line on March 7, 2020. Available at: www.china.org.cn/ china/2020-03/07/content_75785868.htm (accessed on March 28, 2020). www.directivepublications.org Page - 3 The Journal of Clinical Microbiology Editorial
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