Abstract
BackgroundHuman amniotic epithelial cell (hAEC) transplantation holds great promise in treating premature ovarian insufficiency (POI). However, some deficient biological characteristics of hAECs restrict their application.MethodsVitamin C (VC) was added to the culture media of hAECs for 2 weeks. Then, the proliferative ability, migration ability, pluripotency, and self-renewal of VC-treated hAECs (VC-hAECs) were determined. Next, hAECs and VC-hAECs were transplanted into the ovaries of cyclophosphamide (CTX)-induced POI model mice. The ovarian function of POI mice was evaluated after transplantation by counting follicle numbers and measuring the blood levels of AMH, E2, and FSH. The rescue effects of VC-hAECs and hAECs were unveiled by coculturing with CTX-damaged human ovarian granulosa cells (hGCs) and analyzing relative marker expression. Additionally, ovarian marker expression and transplant survival were detected in POI mice after transplantation to verify the beneficial effect of VC-hAECs. The cytokine profiles of VC-hAECs and hAECs were revealed by performing a cytokine array and an ELISA to show their paracrine function.ResultsOur results indicated that VC promoted the proliferation, migration, pluripotency, and self-renewal of hAECs in vitro. The most effective concentration of VC was 50 μg/ml. After transplantation into the POI mouse model, VC-hAECs reversed ovarian function more powerfully than hAECs. Human granulosa cell marker expression in CTX-damaged hGCs was increased after coculture with VC-hAECs compared with hAECs. In the ovaries of the POI mice, ovarian marker expression was greater after VC-hAEC transplantation than after hAEC transplantation. VC-hAECs showed higher transplant survival than hAECs. Furthermore, VC-hAECs secreted more growth factors than hAECs.ConclusionTreatment with VC promoted the proliferation, migration, self-renewal, and paracrine functions of hAECs. Additionally, VC elevated the therapeutic potential of hAECs in treating POI.
Highlights
Premature ovarian insufficiency (POI), which is referred to as premature ovarian failure (POF), is a reversible syndrome affecting the female population under the age of 40 [1]
PBS, 50 μg/ml Vitamin C (VC), and/ or 50 μg/ml Valproic acid (VPA) were added to the culture media of Human amniotic epithelial cell (hAEC) at passage 5 every 24 h
The cell densities of hAECs treated with only VPA and hAECs treated with both VC and VPA were lower than those of hAECs treated with PBS at 7 days
Summary
Premature ovarian insufficiency (POI), which is referred to as premature ovarian failure (POF), is a reversible syndrome affecting the female population under the age of 40 [1]. Accessible treatments for POI, such as hormone replacement therapy and ovulation induction, are not satisfying. Recent studies have been focused on the search for alternative treatments, such as stem cell therapy. Ovarian regeneration after stem cell therapy results from complex and unclear factors. Several studies noted that material transfer between host and donor cells accounts for the rescue effect of stem cell therapy [7, 8]. We cannot rule out the possibility that transplanted stem cells may integrate into host ovaries, differentiate into ovarian cells, and replace the impaired cells of the recipients. Human amniotic epithelial cell (hAEC) transplantation holds great promise in treating premature ovarian insufficiency (POI). Some deficient biological characteristics of hAECs restrict their application
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