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 × 106, 8.5 × 106, and 1.2 × 107/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 × 106, 1.2 × 107, and 2.4 × 107/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 × 107/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 × 107/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 × 106/kg for fertility and early embryonic development, 1.2 × 107/kg for maternal toxicity and 2.4 × 107/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.
Background Based on understanding of placental pathological features and safe medication in pregnancy-associated malaria (PAM), establishment of a stable pregnant mouse infection model with Plasmodium was urgently needed.Methods ICR mice with vaginal plugs detected were randomly divided into post-pregnancy infection (Malaria+) and uninfected pregnancy (Malaria−) cohorts. Age-matched mice that had not been mated were infected as pre-pregnancy infection group (Virgin control), which were subsequently mated with ICR males. All mice were inoculated with 1×106 Plasmodium berghei ANKA-infected RBCs by intraperitoneal injection, and the same amount of saline was given to Malaria− group. We recorded the incidence of adverse pregnancy outcomes and the amounts of offspring in each group.Results The Virgin group mice were unable to conceive normally, and vaginal bleeding, abortion, or stillbirth appeared in the Malaria+ group. The incidence of adverse pregnancy outcomes was extremely high and statistically significant compared with the control (Malaria−) group (P < 0.05), of which placenta exhibited pathological features associated with human gestational malaria.Conclusions The intraperitoneal injection of 1×106 Plasmodium berghei ANKA-infected RBCs could establish a mouse model of post-pregnancy malaria infection.
Backgroud:Based on understanding of placental pathological features and safe medication in pregnancy-associated malaria (PAM), establishment of a stable pregnant mice infection model with Plasmodium was urgently needed. Methods: ICR mice were randomly divided into pre-pregnancy infection, post-pregnancy infection, and uninfected pregnancy cohorts. The mice were inoculated with 1×106 Plasmodium berghei ANKA-infected RBCs by intraperitoneal injection, and the same amount of saline was given to uninfected pregnancy group. We recorded the incidence of adverse pregnancy outcomes and the amounts of offspring in each group. Results: The pre-pregnancy infection group mice were unable to conceive normally, and vaginal bleeding, abortion, or stillbirth appeared in the post-pregnancy infection group. The incidence of adverse pregnancy outcomes was extremely high and statistically significant compared with the control (Malaria-) group (P < 0.05), of which placenta exhibited pathological features associated with human gestational malaria. Conclusions: The intraperitoneal injection of 1×106 Plasmodium berghei ANKA-infected RBCs can establish a murine model of post-pregnancy malaria infection.
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