Human umbilical cord mesenchymal stem cells toxicity and allergy effects: In vivo assessment

• Published in: PloS one Vol. 19; no. 10; p. e0309429
• Main Authors: Cheng, Wu Dong, Bin, Luo, Lin, Zuo Xia, Yu, Ding, Xiang, Ding Ke, Lo, Samantha, Ravichandran, Manickam, Kong, Tham Seng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.10.2024
• Subjects: Acute toxicity; Allergic reaction; Allergic reactions; Allergies; Allergy; Animals; Antigens; Biocompatibility; Biology and Life Sciences; Cell therapy; Clinical trials; Complications and side effects; Drug dosages; Embolism; Experiments; Female; Guinea Pigs; Health aspects; Humans; Hypersensitivity - therapy; In vivo methods and tests; Male; Medical research; Medicine and Health Sciences; Medicine, Experimental; Mesenchymal Stem Cell Transplantation - adverse effects; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mice; Physiological aspects; Pulmonary embolism; Regenerative medicine; Research and Analysis Methods; Risk factors; Safety; Safety and security measures; Safety regulations; Social Sciences; Stem cells; Testing; Toxicity; Toxicity testing; Transplantation; Umbilical cord; Umbilical Cord - cytology; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0309429

Human umbilical cord mesenchymal stem cells (hUCMSCs) hold significant promise across various clinical applications. Therefore, regulatory requirements necessitate a thorough investigation of the hUCMSCs safety before clinical trials and potential allergic reactions after transplantation. Abnormal toxicity test employed mice and guinea pigs dosed daily at 0.5×106 cells and 5×106 cells, respectively for 7 days. Acute toxicity test employed low, medium, and high doses of hUCMSCs injected into mice once, followed by observations for 23 days. In systemic allergy test, guinea pigs received low and high dose of hUCMSCs, with sensitization and excitation stages at day 14 and 21, respectively. The abnormal toxicity test of hUCMSC injections revealed no abnormal reactions over a seven-day observation period, indicating the safety of this administration route. In acute toxicity studies, the high-dose hUCMSCs group resulted in fatalities due to pulmonary embolism. Conversely, the low-dose group exhibited no toxic reactions or deaths. The maximum tolerated dose was determined to be >2×107 cells/kg. Systemic active allergy test showed that high doses of hUCMSC intravenous injections did not induce allergic reactions. This research affirms hUCMSC injections meet safety standards for clinical cell therapy, emphasizing their safe and promising clinical utility.