Reproductive and Developmental Toxicity Assessment of Human Umbilical Cord Mesenchymal Stem Cells in Rats

作者：Li, Xiaobo; Huang, Qijing; Zhang, Xiangxiang; Xie, Changfeng; Liu, Muyun; Yuan, Yueming; Feng, Jianjia; Xing, Haoyu; Ru, Li; Yuan, Zheng; Xu, Zhiyong; Yang, YaoXiang; Long, Yan; Xing, Chengfeng^*; Song, Jianping^*; Hu, Xiang^*; Xu, Qin^*

来源：Frontiers in Cell and Developmental Biology, 2022, 10: 883996.

DOI：10.3389/fcell.2022.883996

• mesenchymal stem cells
• umbilical cord
• reproductive toxicity
• developmental toxicity
• rats

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.

• 单位
  1; 广州中医药大学