Umbilical Cord-derived Mesenchymal Stem Cells (CLV-100) Infusion in Healthy Subjects: a 5-Year Follow-up Study on Safety and Immunomodulatory Effect

Xie Q, Liu R, Jiang J, Peng J, Yang C, Zhang W, Wang S, Song J. What is the impact of human umbilical cord mesenchymal stem cell transplantation on clinical treatment? Stem Cell Res Ther. 2020;11(519):1–13.

Google Scholar 

Shang Y, Guan H, Zhou F. Biological characteristics of umbilical cord mesenchymal stem cells and its therapeutic potential for hematological disorders. Front cell Dev Biol. 2021;9:570179.

Article  PubMed  PubMed Central  Google Scholar 

Zhao T, Liang Q, Meng X, Duan P, Wang F, Li S, et al. Intravenous infusion of umbilical cord mesenchymal stem cells maintains and partially improves visual function in patients with advanced retinitis pigmentosa. Stem Cells Dev. 2020;29(16):1029–37.

Article  PubMed  CAS  Google Scholar 

Song N, Scholtemeijer M, Shah K. Mesenchymal stem cell immunomodulation: mechanisms and therapeutic potential. Trends Pharmacol Sci. 2020;41(9):653–64.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mebarki M, Abadie C, Larghero J, Cras A. Human umbilical cord-derived mesenchymal stem/stromal cells : a promising candidate for the development of advanced therapy medicinal products. 2021;1–10.

Malgieri A, Kantzari E, Patrizi MP, Gambardella S. Bone marrow and umbilical cord blood human mesenchymal stem cells: state of the art. Int J Clin Exp Med. 2010;3(4):248–69.

PubMed  PubMed Central  Google Scholar 

Tesarova L, Jaresova K, Simara P, Koutna I. Umbilical cord-derived mesenchymal stem cells are able to use bFGF treatment and represent a superb tool for immunosuppressive clinical applications. Int J Mol Sci. 2020;21:5366.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Yun J-W, Ahn JH, Kwon E, Kim S-H, Kim H, Jang J-J, et al. Human umbilical cord-derived mesenchymal stem cells in acute liver injury: hepatoprotective efficacy, subchronic toxicity, tumorigenicity, and biodistribution. Regul Toxicol Pharmacol. 2016;81:437–47.

Article  PubMed  CAS  Google Scholar 

Chen G, Yue A, Ruan Z, Yin Y, Wang R, Ren Y, et al. Human umbilical cord-derived mesenchymal stem cells do not undergo malignant transformation during long-term culturing in serum-free medium. PLoS One. 2014;9(6):e98565.

Article  PubMed  PubMed Central  Google Scholar 

Chin S-P, Saffery NS, Then K-Y, Cheong S-K. Preclinical assessments of safety and tumorigenicity of very high doses of allogeneic human umbilical cord mesenchymal stem cells. In Vitro Cell Dev Biol Anim. 2024.

Hu J, Wang Y, Gong H, Yu C, Guo C, Wang F, et al. Long term effect and safety of Wharton’s jelly-derived mesenchymal stem cells on type 2 diabetes. Exp Ther Med. 2016;12:1857–66.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Li T-T, Zhang B, Fang H, Shi M, Yao W-Q, Li Y, et al. Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trial. EBioMedicine. 2023;92:104600.

Article  PubMed  PubMed Central  Google Scholar 

Awidi A, Al SA, El AN, Alqudah M, Jamali F, Nazer F, et al. Safety and potential efficacy of expanded mesenchymal stromal cells of bone marrow and umbilical cord origins in patients with chronic spinal cord injuries: a phase I/II study. Cytotherapy. 2024;26:825–31.

Article  PubMed  CAS  Google Scholar 

Wang D, Niu L, Feng X, Yuan X, Zhao S, Zhang H, et al. Long-term safety of umbilical cord mesenchymal stem cells transplantation for systemic lupus erythematosus: a 6-year follow-up study. Clin Exp Med. 2017;17(3):333–40.

Article  PubMed  CAS  Google Scholar 

Shi M, Li Y-Y, Xu R-N, Meng F-P, Yu S-J, Fu J-L, et al. Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial. Hepatol Int. 2021;15(6):1431–41.

Article  PubMed  Google Scholar 

Lee JS, Hong JM, Moon GJ, Lee PH, Ahn YH, Bang OY, et al. A long-term follow-up study of intravenous autologous mesenchymal stem cell transplantation in patients with ischemic stroke. Stem Cells. 2010;28(6):1099–106.

Article  PubMed  Google Scholar 

Chin S-P, Mohd-Shahrizal M-Y, Liyana M-Z, Then KY, Cheong SK. High dose of intravenous allogeneic umbilical cord-derived mesenchymal stem cells (CLV-100) infusion displays better immunomodulatory effect among healthy volunteers: a phase 1 clinical study. Stem Cells Int. 2020;2020:8877003.

Article  PubMed  PubMed Central  Google Scholar 

Tai L, Saffery NS, Chin SP, Cheong SK. Secretome profile of TNF-α-induced human umbilical cord mesenchymal stem cells unveils biological processes relevant to skin wound healing. Regen Med. 2023;18(11):839–56.

Article  PubMed  CAS  Google Scholar 

Public Service Delivery and Local Government. In: The Elderly/Senior Citizens. My Government. 2021. https://www.malaysia.gov.my/portal/content/27752. Accessed 25 Oct 2023.

Nagpal M, Singh S, Singh P, Chauhan P, Zaidi MA. Tumor markers: a diagnostic tool. Natl J Maxillofac Surg. 2016;7(1):17–20.

Article  PubMed  PubMed Central  Google Scholar 

Ballehaninna UK, Chamberlain RS. Serum CA 19–9 as a biomarker for pancreatic cancer—a comprehensive review. Indian J Surg Oncol. 2011;2(2):88–100.

Article  PubMed  PubMed Central  Google Scholar 

Kankanala VL, Zubair M, Mukkamalla SKR. Carcinoembryonic antigen. [Updated 2024 Dec 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK578172/

Touitou Y, Proust J, Klinger E, Nakache JP, Huard D, Sachet A. Cumulative effects of age and pathology on plasma carcinoembryonic antigen in an unselected elderly population. Eur J Cancer Clin Oncol. 1984;20(3):369–74.

Article  PubMed  CAS  Google Scholar 

Li J, Wu Z, Zhao L, Liu Y, Su Y, Gong X, et al. The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy. Stem Cell Res Ther. 2023;14(1):1–14.

Article  Google Scholar 

Jiang W, Xu J. Immune modulation by mesenchymal stem cells. Cell Prolif. 2020;53(1):e12712.

Article  PubMed  Google Scholar 

Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev. 2018;281(1):8–27.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Volarevic V, Al-Qahtani A, Arsenijevic N, Pajovic S, Lukic ML. Interleukin-1 receptor antagonist (IL-1Ra) and IL-1Ra producing mesenchymal stem cells as modulators of diabetogenesis. Autoimmunity. 2010;43(4):255–63.

Article  PubMed  CAS  Google Scholar 

Almeida-Santiago C, Quevedo-Abeledo JC, Hernández-Hernández V, de Vera-González A, Gonzalez-Delgado A, González-Gay MÁ, et al. Interleukin 1 receptor antagonist relation to cardiovascular disease risk in patients with rheumatoid arthritis. Sci Rep. 2022;12(1):13698.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Luotola K. IL-1 receptor antagonist (IL-1Ra) levels and management of metabolic disorders. Nutrients. 2022;14(16):3422.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ferrucci L, Corsi A, Lauretani F, Bandinelli S, Bartali B, Taub DD, et al. The origins of age-related proinflammatory state. Blood. 2005;105(6):2294–9.

Article  PubMed  CAS  Google Scholar 

Wilcox G. Insulin and insulin resistance. Clin Biochem Rev. 2005;26(2):19–39.

PubMed  PubMed Central  Google Scholar 

He X, Ai S, Guo W, Yang Y, Wang Z, Jiang D, et al. Umbilical cord-derived mesenchymal stem (stromal) cells for treatment of severe sepsis: a phase 1 clinical trial. Transl Res [Internet]. 2018. https://doi.org/10.1016/j.trsl.2018.04.006.

Kazemian S, Ahmadi R, Rafiei A, Azadegan-Dehkordi F, Khaledifar A, Abdollahpour-Alitappeh M, et al. The serum levels of IL-36 in patients with coronary artery disease and their correlation with the serum levels of IL-32, IL-6, TNF-α, and oxidative stress. Int Arch Allergy Immunol. 2022;183(10):1137–45.

Article  PubMed  CAS  Google Scholar 

Mohammadi M, Gozashti MH, Aghadavood M, Mehdizadeh MR, Hayatbakhsh MM. Clinical significance of serum IL-6 and TNF-α levels in patients with metabolic syndrome. Reports Biochem Mol Biol. 2017;6(1):74–9.

CAS  Google Scholar 

Wyczalkowska-Tomasik A, Czarkowska-Paczek B, Zielenkiewicz M, Paczek L. Inflammatory markers change with age, but do not fall beyond reported normal ranges. Arch Immunol Ther Exp (Warsz). 2016;64(3):249–54.

Article  PubMed  CAS 

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