Evaluation of safety and efficacy of amniotic mesenchymal stem cells for POI in animals

Abstract The efficacy of human amniotic mesenchymal stem cells (hAMSCs) ovarian injection for improving ovarian function of POI (Premature ovarian failure) patients has been showed in some reports. However, the safety and efficacy of the hAMSCs vein injection remains unclear. In this study, we evaluate the safety and efficacy of hAMSCs intravenous injection in cynomolgus macaques and SD rats, and to provide the evidence for clinical trials. The hAMSCs were transplanted three times in SD rats at low, medium and high doses, respectively. The animal behavior, biochemical and biophysical parameters were routinely monitored on a 2-month period posttransplantation, and the histopathologic examinations were also performed. Experiments on the acute toxicity, allergy test and hemolysis test showed that hAMSCs possesses good biocompatibility. Our results showed that maximum tolerated dose of hAMSCs in SD rats was 4.0×107cells/kg. The maximum safe dose with three injections of hAMSCs in SD rats was 5.0×106cells/kg. In addition, the results demonstrated that hAMSCs could restore the POI rats ovarian function after twice injected with 2.5×106cells/kg or 5.0×106cells/kg dose, which through improving the disturbed estrous cycle, hormone levels and ovarian lesion induced by pZP3. In conclusion, the preclinical results suggested that the transplantation of hAMSCs is safe and efficacious for SD rats at 5.0×106cells/kg and lower doses.