PMID- 35185283 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230202 IS - 0920-9069 (Print) IS - 1573-0778 (Electronic) IS - 0920-9069 (Linking) VI - 74 IP - 1 DP - 2022 Feb TI - hUC-MSCs: evaluation of acute and long-term routine toxicity testing in mice and rats. PG - 17-29 LID - 10.1007/s10616-021-00502-2 [doi] AB - Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are present in human umbilical connective tissue and can differentiate into various cell types. Our previous studies have proved that hUC-MSCs do not lead to allergies and tumorigenesis. In the present study, the acute and long-term toxicity of hUC-MSCs in mice and rats was evaluated. The acute toxicity of hUC-MSCs was assessed in 8-week-old mice receiving two caudal intravenous (i.v.) injections of hUC-MSCs at the maximum tolerated dose of 1.5 x 10(7) cells/kg with an interval of 8 h and the observation period sustained for 14 days. For the long-term toxicity evaluation, rats were randomly divided into control, low-dose (3.0 x 10(5) cells/kg), mid-dose (1.5 x 10(6) cells/kg), and high-dose (7.5 x 10(6) cells/kg) groups, which were treated with hUC-MSCs via a caudal i.v. injection every 3 days for 90 days. Weight and food intake evaluation was performed for all rats for 2 weeks after the hUC-MSC administration. The animals were then sacrificed for hematological, blood biochemical, and pathological analyses, as well as organ index determination. We observed no obvious acute toxicity of hUC-MSCs in mice at the maximum tolerated dose. Long-term toxicity tests in rats showed no significant differences between HUC-MSC-treated and control groups in the following parameters: body weight, hematological and blood biochemical parameters, and histopathologic changes in the heart, liver, kidneys, and lungs. This study provides evidence of the safety of i.v. hUC-MSCs infusion for future clinical therapies. CI - (c) The Author(s), under exclusive licence to Springer Nature B.V. 2022. FAU - Xu, Jianwei AU - Xu J AD - National Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Center for Tissue Engineering and Stem Cell Research, Guizhou Province Key Laboratory of Regenerative Medicine, Guizhou Medical University, Guiyang, China. GRID: grid.413458.f. ISNI: 0000 0000 9330 9891 AD - Key Laboratory of Adult Stem Cell Translational Research, Chinese Academy of Medical Sciences, Guiyang, China. AD - Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, Guiyang, China. GRID: grid.413458.f. ISNI: 0000 0000 9330 9891 FAU - Liu, Gang AU - Liu G AD - Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, Guiyang, China. GRID: grid.413458.f. ISNI: 0000 0000 9330 9891 FAU - Wang, Xianyao AU - Wang X AD - National Guizhou Joint Engineering Laboratory for Cell Engineering and Biomedicine Technique, Center for Tissue Engineering and Stem Cell Research, Guizhou Province Key Laboratory of Regenerative Medicine, Guizhou Medical University, Guiyang, China. GRID: grid.413458.f. ISNI: 0000 0000 9330 9891 FAU - Hu, Ya'nan AU - Hu Y AD - Department of Cell Biology, Medical College of Soochow University, Suzhou, China. GRID: grid.263761.7. ISNI: 0000 0001 0198 0694 FAU - Luo, Hongyang AU - Luo H AD - Department of Otorhinolaryngology, People's Hospital of Wudang District, Guiyang, China. FAU - Ye, Lan AU - Ye L AD - Department of Pharmacology, School of Basic Medicine, Guizhou Medical University, Guiyang, China. GRID: grid.413458.f. ISNI: 0000 0000 9330 9891 FAU - Feng, Zhanhui AU - Feng Z AD - Neurological Department, Affiliated Hospital of Guizhou Medical University, Guiyang, China. GRID: grid.452244.1 FAU - Li, Chen AU - Li C AD - Department of Oncology, General Hospital of the Yangtze River Shipping, Wuhan, China. FAU - Kuang, Menglan AU - Kuang M AD - School of Pharmacy, Guizhou Medical University, Guiyang, China. GRID: grid.413458.f. ISNI: 0000 0000 9330 9891 FAU - Zhang, Lijuan AU - Zhang L AD - School of Nursing, Guizhou Medical University, Guiyang, China. GRID: grid.413458.f. ISNI: 0000 0000 9330 9891 FAU - Zhou, Yixia AU - Zhou Y AD - School of Nursing, Guizhou University of Traditional Chinese Medicine, 9# Beijing Road, Guiyang, China. GRID: grid.443382.a. ISNI: 0000 0004 1804 268X AD - Department of Nursing, The Affiliated Hospital of Guizhou Medical University, Guiyang, China. GRID: grid.452244.1 FAU - Qi, Xiaolan AU - Qi X AD - Key Laboratory of Endemic and Ethnic Diseases (Guizhou Medical University), Ministry of Education, 9# Beijing Road, Guiyang, People's Republic of China. GRID: grid.413458.f. ISNI: 0000 0000 9330 9891 AD - Key Laboratory of Medical Molecular Biology (Guizhou Medical University), Guiyang, 550004 People's Republic of China. GRID: grid.413458.f. ISNI: 0000 0000 9330 9891 LA - eng PT - Journal Article DEP - 20220105 PL - United States TA - Cytotechnology JT - Cytotechnology JID - 8807027 PMC - PMC8817012 OTO - NOTNLM OT - Acute toxicity OT - Biotransformation and toxicokinetics OT - Human umbilical cord-derived mesenchymal stem cells OT - Long-term toxicity OT - Safety evaluation COIS- Conflict of interestThe authors declare no potential conflicts of interest,All authors state that they have nothing to disclose. EDAT- 2022/02/22 06:00 MHDA- 2022/02/22 06:01 PMCR- 2023/02/01 CRDT- 2022/02/21 05:59 PHST- 2021/05/21 00:00 [received] PHST- 2021/10/17 00:00 [accepted] PHST- 2022/02/21 05:59 [entrez] PHST- 2022/02/22 06:00 [pubmed] PHST- 2022/02/22 06:01 [medline] PHST- 2023/02/01 00:00 [pmc-release] AID - 502 [pii] AID - 10.1007/s10616-021-00502-2 [doi] PST - ppublish SO - Cytotechnology. 2022 Feb;74(1):17-29. doi: 10.1007/s10616-021-00502-2. Epub 2022 Jan 5.