PMID- 35663387 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231105 IS - 2296-634X (Print) IS - 2296-634X (Electronic) IS - 2296-634X (Linking) VI - 10 DP - 2022 TI - Reproductive and Developmental Toxicity Assessment of Human Umbilical Cord Mesenchymal Stem Cells in Rats. PG - 883996 LID - 10.3389/fcell.2022.883996 [doi] LID - 883996 AB - Objective: Human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown very attractive potential in clinical applications for the treatment of various diseases. However, the data about the reproductive and developmental toxicity of hUC-MSCs remains insufficient. Thus, we assessed the potential effects of intravenous injection of hUC-MSCs on reproduction and development in Sprague-Dawley rats. Methods: In the fertility and early embryonic development study, hUC-MSCs were administered at dose levels of 0, 6.0 x 10(6), 8.5 x 10(6), and 1.2 x 10(7)/kg to male and female rats during the pre-mating, mating and gestation period. In the embryo-fetal development study, the pregnant female rats received 0, 6.0 x 10(6), 1.2 x 10(7), and 2.4 x 10(7)/kg of hUC-MSCs from gestation days (GD) 6-15. Assessments made included mortality, clinical observations, body weight, food consumption, fertility parameters of male and female, litter, and fetus parameters, etc. Results: No hUC-MSCs-related toxicity was observed on the fertility of male and female rats, and no teratogenic effect on fetuses. hUC-MSCs at 1.2 x 10(7)/kg caused a mildly decrease in body weight gain of male rats, transient listlessness, tachypnea, and hematuria symptoms in pregnant female rats. Death was observed in part of the pregnant females at a dose of 2.4 x 10(7)/kg, which could be due to pulmonary embolism. Conclusion: Based on the results of the studies, the no-observed-adverse-effect levels (NOAELs) are 8.5 x 10(6)/kg for fertility and early embryonic development, 1.2 x 10(7)/kg for maternal toxicity and 2.4 x 10(7)/kg for embryo-fetal development in rats intravenous injected with hUC-MSCs, which are equivalent to 8.5-fold, 12-fold, and 24-fold respectively of its clinical dosage in humans. These findings may provide a rational basis for human health risk assessment of hUC-MSCs. CI - Copyright (c) 2022 Li, Huang, Zhang, Xie, Liu, Yuan, Feng, Xing, Ru, Yuan, Xu, Yang, Long, Xing, Song, Hu and Xu. FAU - Li, Xiaobo AU - Li X AD - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Country Sci-Tech Industrial Park, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Huang, Qijing AU - Huang Q AD - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Zhang, Xiangxiang AU - Zhang X AD - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Xie, Changfeng AU - Xie C AD - Shenzhen Beike Biotechnology Co., Ltd., Shenzhen, China. FAU - Liu, Muyun AU - Liu M AD - Shenzhen Beike Biotechnology Co., Ltd., Shenzhen, China. FAU - Yuan, Yueming AU - Yuan Y AD - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Country Sci-Tech Industrial Park, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Feng, Jianjia AU - Feng J AD - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Xing, Haoyu AU - Xing H AD - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Ru, Li AU - Ru L AD - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. AD - Country Sci-Tech Industrial Park, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Yuan, Zheng AU - Yuan Z AD - Country Sci-Tech Industrial Park, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Xu, Zhiyong AU - Xu Z AD - Country Sci-Tech Industrial Park, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Yang, YaoXiang AU - Yang Y AD - Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China. FAU - Long, Yan AU - Long Y AD - Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou, China. FAU - Xing, Chengfeng AU - Xing C AD - Country Sci-Tech Industrial Park, Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Song, Jianping AU - Song J AD - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. FAU - Hu, Xiang AU - Hu X AD - Shenzhen Beike Biotechnology Co., Ltd., Shenzhen, China. FAU - Xu, Qin AU - Xu Q AD - Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China. AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. LA - eng PT - Journal Article DEP - 20220519 PL - Switzerland TA - Front Cell Dev Biol JT - Frontiers in cell and developmental biology JID - 101630250 PMC - PMC9160830 OTO - NOTNLM OT - developmental toxicity OT - mesenchymal stem cells OT - rats OT - reproductive toxicity OT - umbilical cord COIS- Authors CX, ML and XH were employed by Shenzhen Beike Biotechnology Co., Ltd. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/06/07 06:00 MHDA- 2022/06/07 06:01 PMCR- 2022/01/01 CRDT- 2022/06/06 13:59 PHST- 2022/02/25 00:00 [received] PHST- 2022/03/28 00:00 [accepted] PHST- 2022/06/06 13:59 [entrez] PHST- 2022/06/07 06:00 [pubmed] PHST- 2022/06/07 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 883996 [pii] AID - 10.3389/fcell.2022.883996 [doi] PST - epublish SO - Front Cell Dev Biol. 2022 May 19;10:883996. doi: 10.3389/fcell.2022.883996. eCollection 2022.