BACKGROUND Premature ovarian insufficiency(POI)and premature ovarian failure(POF)have become one of the major problems threatening women of childbearing age.Studies have shown that stem cells transplanted from bone ma...BACKGROUND Premature ovarian insufficiency(POI)and premature ovarian failure(POF)have become one of the major problems threatening women of childbearing age.Studies have shown that stem cells transplanted from bone marrow,umbilical cord,peripheral blood and amniotic fluid can migrate and proliferate to the ovary,promote ovarian function repair,increase the number of follicles and granulosa cells at all levels of ovary,improve endocrine function,and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.AIM To study the ability of human umbilical cord mesenchymal stem cells(hUCMSCs)to repair ovarian injury after chemotherapy.METHODS A total of 110 female BALB/c mice(aged 7-8 wk old)with body masses of 16.0-20.0 g were selected.The mice were fed until 12 wk of age,and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice.Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight:model group,positive control group and hUCMSC group,and each group had 25 mice.Another 25 mice were used as negative controls.The mice in the hUCMSC group were injected with hUCMSCs in the tail vein,and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein.On the 1^st,15^th,30^th,45^th,and 60^th days after intravenous administration,vaginal smears were made to monitor the estrous cycles of the mice.The ovaries were weighed,and pathological sections were made to observe the morphology of the follicles;blood samples were collected to monitor the concentration of sex hormones(oestradiol and follicle-stimulating hormone).RESULTS The estrous cycles of the model group mice were disrupted throughout the experiment.Mice in the hUCMSC group and the positive control group resumed normal estrous cycles.The ovarian weight of the model group mice continued to decline.The ovarian wei展开更多
BACKGROUND Premature ovarian failure(POF)affects many adult women less than 40 years of age and leads to infertility.According to previous reports,various tissue-specific stem cells can restore ovarian function and fo...BACKGROUND Premature ovarian failure(POF)affects many adult women less than 40 years of age and leads to infertility.According to previous reports,various tissue-specific stem cells can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF.Human embryonic stem cells(ES)provide an alternative source for mesenchymal stem cells(MSCs)because of their similarities in phenotype and immunomodulatory and anti-inflammatory characteristics.Embryonic stem cell-derived mesenchymal stem cells(ES-MSCs)are attractive candidates for regenerative medicine because of their high proliferation and lack of barriers for harvesting tissue-specific MSCs.However,possible therapeutic effects and underlying mechanisms of transplanted ES-MSCs on cyclophosphamide and busulfan-induced mouse ovarian damage have not been evaluated.AIM To evaluate ES-MSCs vs bone marrow-derived mesenchymal stem cells(BMMSCs)in restoring ovarian function in a mouse model of chemotherapy-induced premature ovarian failure.METHODS Female mice received intraperitoneal injections of different doses of cyclophosphamide and busulfan to induce POF.Either human ES-MSCs or BMMSCs were transplanted into these mice.Ten days after the mice were injected with cyclophosphamide and busulfan and 4 wk after transplantation of the ESMSCs and/or BM-MSCs,we evaluated body weight,estrous cyclicity,folliclestimulating hormone and estradiol hormone concentrations and follicle count were used to evaluate the POF model and cell transplantation.Moreover,terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling,real-time PCR,Western blot analysis and immunohistochemistry and mating was used to evaluate cell transplantation.Enzyme-linked immunosorbent assay was used to analyze vascular endothelial growth factor,insulin-like growth factor 2 and hepatocyte growth factor levels in ES-MSC condition medium in order to investigate the mechanisms that underlie their function.RESULTS The human ES-MSCs significantly restored hormone s展开更多
文摘BACKGROUND Premature ovarian insufficiency(POI)and premature ovarian failure(POF)have become one of the major problems threatening women of childbearing age.Studies have shown that stem cells transplanted from bone marrow,umbilical cord,peripheral blood and amniotic fluid can migrate and proliferate to the ovary,promote ovarian function repair,increase the number of follicles and granulosa cells at all levels of ovary,improve endocrine function,and can differentiate into oocytes in specific ovarian environment to restore fertility to some extent.AIM To study the ability of human umbilical cord mesenchymal stem cells(hUCMSCs)to repair ovarian injury after chemotherapy.METHODS A total of 110 female BALB/c mice(aged 7-8 wk old)with body masses of 16.0-20.0 g were selected.The mice were fed until 12 wk of age,and cyclophosphamide was administered by intraperitoneal injection for 14 consecutive days to induce premature ovarian failure in mice.Seventy-five mice with estrous cycle disorder were screened and randomly divided into 3 groups according to their body weight:model group,positive control group and hUCMSC group,and each group had 25 mice.Another 25 mice were used as negative controls.The mice in the hUCMSC group were injected with hUCMSCs in the tail vein,and the mice in the positive control group were given an oestradiol valerate solution and a medroxyprogesterone acetate solution in the tail vein.On the 1^st,15^th,30^th,45^th,and 60^th days after intravenous administration,vaginal smears were made to monitor the estrous cycles of the mice.The ovaries were weighed,and pathological sections were made to observe the morphology of the follicles;blood samples were collected to monitor the concentration of sex hormones(oestradiol and follicle-stimulating hormone).RESULTS The estrous cycles of the model group mice were disrupted throughout the experiment.Mice in the hUCMSC group and the positive control group resumed normal estrous cycles.The ovarian weight of the model group mice continued to decline.The ovarian wei
文摘BACKGROUND Premature ovarian failure(POF)affects many adult women less than 40 years of age and leads to infertility.According to previous reports,various tissue-specific stem cells can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF.Human embryonic stem cells(ES)provide an alternative source for mesenchymal stem cells(MSCs)because of their similarities in phenotype and immunomodulatory and anti-inflammatory characteristics.Embryonic stem cell-derived mesenchymal stem cells(ES-MSCs)are attractive candidates for regenerative medicine because of their high proliferation and lack of barriers for harvesting tissue-specific MSCs.However,possible therapeutic effects and underlying mechanisms of transplanted ES-MSCs on cyclophosphamide and busulfan-induced mouse ovarian damage have not been evaluated.AIM To evaluate ES-MSCs vs bone marrow-derived mesenchymal stem cells(BMMSCs)in restoring ovarian function in a mouse model of chemotherapy-induced premature ovarian failure.METHODS Female mice received intraperitoneal injections of different doses of cyclophosphamide and busulfan to induce POF.Either human ES-MSCs or BMMSCs were transplanted into these mice.Ten days after the mice were injected with cyclophosphamide and busulfan and 4 wk after transplantation of the ESMSCs and/or BM-MSCs,we evaluated body weight,estrous cyclicity,folliclestimulating hormone and estradiol hormone concentrations and follicle count were used to evaluate the POF model and cell transplantation.Moreover,terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling,real-time PCR,Western blot analysis and immunohistochemistry and mating was used to evaluate cell transplantation.Enzyme-linked immunosorbent assay was used to analyze vascular endothelial growth factor,insulin-like growth factor 2 and hepatocyte growth factor levels in ES-MSC condition medium in order to investigate the mechanisms that underlie their function.RESULTS The human ES-MSCs significantly restored hormone s
