BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that me...BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that menstrual-derived stromal stem cells(MenSCs),with high proliferative capacity and self-renewal ability,have a powerful therapeutic effect in patients with severe IUA.However,safety assessment of MenSCs transplantation is essential for its further application.AIM To evaluate the short-,medium-,and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA,with a focus on toxicity and tumorigenicity.METHODS MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model,for 3 d,3 mo,and 6 mo separately,to monitor the corresponding acute,sub-chronic,and chronic effects.Healthy rats of the same age served as negative controls.Toxicity effects were evaluated by body weight,organ weight,histopathology,hematology,and biochemistry tests.Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.RESULTS Compared with the same week-old control group,all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight,mainorgan weight,or blood cell composition during the acute,sub-chronic,and chronic observation periods.At the same time,serum biochemical tests showed no adverse effects on metabolism or liver and kidney function.After 4 wk of subcutaneous injection of Men SCs in Balb/c-nu nude mice,no tumor formation or cell metastasis was observed.Moreover,there was no tumor colony formation of Men SCs during soft agar culture in vitro.CONCLUSION There is no acute,sub-chronic,or chronic poisoning,infection,tumorigenesis,or endometriosis in rats with IUA after Men SC transplantation.The above results suggest that intrauterine transplantation of Men SCs is safe for endometrial treatment.展开更多
Damage in central nervous system plays an important role in biological life and causes severe paralysis of limbs and some organs. There are solutions to problems that can be a great revolution in the transplanted spin...Damage in central nervous system plays an important role in biological life and causes severe paralysis of limbs and some organs. There are solutions to problems that can be a great revolution in the transplanted spinal cord and nerve injuries. Schwann cells (SCs) have important roles in development, myelination and regeneration in the peripheral nervous system. The applications of SCs in regenerative medicine are limited because of slow growth rate and difficulties in harvesting. Critical to the hypothesis is the experimental fact that human endometrial-derived stem cells (hEnSCs) as multipotent accessible source of cells are known as useful cell candidates in the field of nerve tissue engineering. We decided to use the three-dimensional culture of Schwann cells differentiated from endometrial stem cell in fibrin gel. In this study, we investigate the expression of differentiated Schwann cell markers by exposing of endometrial stem cells with induction media including FGF2/FSK/HRG/RA. Using immunocytochemistry, we show that differentiated cells express S100 and P75 markers. These results show that for the first time, human endometrial stem cells can be differentiated into Schwann cells in 2D and 3D culture. These novel differentiated cells in fibrin gel might open new opportunities for the management of cell survival and neurotrophic potential in tissue engineering approaches for nerve repair.展开更多
BACKGROUND Type 1 diabetes(T1D),a chronic metabolic and autoimmune disease,seriously endangers human health.In recent years,mesenchymal stem cell(MSC)transplantation has become an effective treatment for diabetes.Mens...BACKGROUND Type 1 diabetes(T1D),a chronic metabolic and autoimmune disease,seriously endangers human health.In recent years,mesenchymal stem cell(MSC)transplantation has become an effective treatment for diabetes.Menstrual bloodderived endometrial stem cells(MenSC),a novel MSC type derived from the decidual endometrium during menstruation,are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure,high proliferation rate and high immunomodulation capacity.AIM To comprehensively compare the effects of MenSC and umbilical cord-derived MSC(UcMSC)transplantation on T1D treatment,to further explore the potential mechanism of MSC-based therapies in T1D,and to provide support for the clinical application of MSC in diabetes treatment.METHODS A conventional streptozotocin-induced T1D mouse model was established,and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected.The morphological and functional changes in the pancreas,liver,kidney,and spleen were analyzed by routine histological and immunohistochemical examinations.Changes in the serum cytokine levels in the model mice were assessed by protein arrays.The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot.RESULTS MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice.Immunofluorescence analysis revealed that the numbers of insulin+and CD31+cells in the pancreas were significantly increased in MSC-treated mice compared with control mice.Subsequent western blot analysis also showed that vascular endothelial growth factor(VEGF),Bcl2,Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice.Additionally,protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferonγand tumor necrosis factorαand upre展开更多
BACKGROUND Polycystic ovary syndrome(PCOS)is an endocrine disease that combines metabolic,reproductive,and psychological dysfunctions.Ovulation disorders and impaired endometrial receptivity in PCOS can cause infertil...BACKGROUND Polycystic ovary syndrome(PCOS)is an endocrine disease that combines metabolic,reproductive,and psychological dysfunctions.Ovulation disorders and impaired endometrial receptivity in PCOS can cause infertility.Insulin resistance(IR)is a pathological state of inadequate response to insulin that affects reproduction in PCOS,as damage caused by IR at the endometrial level becomes an obstacle for embryo implantation.Reversing IR resulted in spontaneous pregnancies in PCOS patients,indicating that metabolic corrections improve endometrial dysfunctions.Mesenchymal stem-cell treatment has also corrected endometrial quality and lead to pregnancies in patients with Asherman’s syndrome.We propose a combination of nutritional intervention with the surgical placement of stem cells to improve endometrial quality to achieve pregnancy in a PCOS patient undergoing in vitro fertilization(IVF)treatment.CASE SUMMARY After two failed IVF cycles,a metabolic intervention,consisting of a ketogenic diet with daily consumption of 50 g of carbohydrates(CH),was indicated until pregnancy.Metabolic Syndrome was assessed using the Harmonizing Definition(3 of 5 pathologies:Central obesity,hypertension,hyperglycemia,hypertriglyceridemia,and dyslipidemia),and the Homeostatic Model Assessment of IR(HOMA-IR)was used to measure the level of IR.Once IR improved,endometrial quality improved.However,two day 5-thawed embryos(euploid,donated oocyte–partner's sperm)failed to implant,suggesting endometrial quality improvement was insufficient.Therefore,transmyometrial implantation of mesenchymal stem cells from the stromal vascular fraction of adipose tissue was performed to enrich the endometrial stem cell niche.Minimal endometrial mean thickness for embryo transfer(6.9 mm)was achieved three months after stem cell treatment and continuous dietary control of IR.Two euploid-day 5-thawed embryos(donated oocyte–partner's sperm)were transferred,and embryo implantation was confirmed on day 14 byβ-hCG serum levels.Currently,a 37 wk baby girl i展开更多
Background: Rhizoma drynariae is a traditional Chinese medicine used in orthopedics and traumatology, but its effect on endometrial receptivity remains unknown. Aims and Objectives: To observe effect of Rhizoma drynar...Background: Rhizoma drynariae is a traditional Chinese medicine used in orthopedics and traumatology, but its effect on endometrial receptivity remains unknown. Aims and Objectives: To observe effect of Rhizoma drynariae and its main components on endometrial receptivity in a mus model of dysfunctional embryo implantation. Materials and Methods: Mus models were established by the Gn RHa+HMG+HCG method. Normal mus receiving saline were used as controls and the remaining six groups were: model receiving saline, progynova, aspirin, Rhizoma drynariae, osteopractic total flavone, and naringin. Pinopodes in uterine endometrium were examined by scanning electron microscopy. Stem cell factor(SCF) m RNA expressions was determined by real-time RT-PCR, and estrogen receptor α(ERα), progesterone receptor(PR) by immunohistochemistry. Results: In the model group, surface morphology of endometrium was heterogeneous, without obvious pinopodes. In the Rhizoma drynaria and progynova groups, pinopodes were abundant. Compared with the blank group, model group had lower levels of SCF(-47%), ERα(-63%) and PR(-50%)(all P<0.05). In comparison, Rhizoma drynariae group had higher levels of SCF(+73%), ERα(+118%) and PR(+101%)(all P<0.01). The individual main components of Rhizoma drynariae had variable efficacy. Conclusion: Rhizoma drynariae could improve endometrial receptivity of mouse models of dysfunctional embryo implantation as shown by increased numbers of pinopodes and higher levers of SCF, ERα, PR compared with the model group.展开更多
基金Supported by the National Key Research and Development Program,No.2018YFC1002105the Key Research and Development Program of Liaoning Province,No.2018020222the Major Special Construction Plan for Discipline Construction Project of China Medical University,No.3110118033。
文摘BACKGROUND Intrauterine adhesion(IUA)can cause serious damage to women’s reproductive health,yet current treatment methods are difficult to achieve satisfactory results.In our previous studies,we demonstrated that menstrual-derived stromal stem cells(MenSCs),with high proliferative capacity and self-renewal ability,have a powerful therapeutic effect in patients with severe IUA.However,safety assessment of MenSCs transplantation is essential for its further application.AIM To evaluate the short-,medium-,and long-term biosafety of MenSCs via intrauterine transplantation in a rat model of IUA,with a focus on toxicity and tumorigenicity.METHODS MenSCs were injected into the sub-serosal layer of the uterus in an IUA rat model,for 3 d,3 mo,and 6 mo separately,to monitor the corresponding acute,sub-chronic,and chronic effects.Healthy rats of the same age served as negative controls.Toxicity effects were evaluated by body weight,organ weight,histopathology,hematology,and biochemistry tests.Tumorigenicity of MenSCs was investigated in Balb/c-nu mice in vivo and by colony formation assays in vitro.RESULTS Compared with the same week-old control group,all of the IUA rats receiving MenSC transplantation demonstrated no obvious changes in body weight,mainorgan weight,or blood cell composition during the acute,sub-chronic,and chronic observation periods.At the same time,serum biochemical tests showed no adverse effects on metabolism or liver and kidney function.After 4 wk of subcutaneous injection of Men SCs in Balb/c-nu nude mice,no tumor formation or cell metastasis was observed.Moreover,there was no tumor colony formation of Men SCs during soft agar culture in vitro.CONCLUSION There is no acute,sub-chronic,or chronic poisoning,infection,tumorigenesis,or endometriosis in rats with IUA after Men SC transplantation.The above results suggest that intrauterine transplantation of Men SCs is safe for endometrial treatment.
文摘Damage in central nervous system plays an important role in biological life and causes severe paralysis of limbs and some organs. There are solutions to problems that can be a great revolution in the transplanted spinal cord and nerve injuries. Schwann cells (SCs) have important roles in development, myelination and regeneration in the peripheral nervous system. The applications of SCs in regenerative medicine are limited because of slow growth rate and difficulties in harvesting. Critical to the hypothesis is the experimental fact that human endometrial-derived stem cells (hEnSCs) as multipotent accessible source of cells are known as useful cell candidates in the field of nerve tissue engineering. We decided to use the three-dimensional culture of Schwann cells differentiated from endometrial stem cell in fibrin gel. In this study, we investigate the expression of differentiated Schwann cell markers by exposing of endometrial stem cells with induction media including FGF2/FSK/HRG/RA. Using immunocytochemistry, we show that differentiated cells express S100 and P75 markers. These results show that for the first time, human endometrial stem cells can be differentiated into Schwann cells in 2D and 3D culture. These novel differentiated cells in fibrin gel might open new opportunities for the management of cell survival and neurotrophic potential in tissue engineering approaches for nerve repair.
基金Henan Province Foundation of China,No.202300410307 and No.212102310611Xinxiang City Foundation of China,No.GG2020009.
文摘BACKGROUND Type 1 diabetes(T1D),a chronic metabolic and autoimmune disease,seriously endangers human health.In recent years,mesenchymal stem cell(MSC)transplantation has become an effective treatment for diabetes.Menstrual bloodderived endometrial stem cells(MenSC),a novel MSC type derived from the decidual endometrium during menstruation,are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure,high proliferation rate and high immunomodulation capacity.AIM To comprehensively compare the effects of MenSC and umbilical cord-derived MSC(UcMSC)transplantation on T1D treatment,to further explore the potential mechanism of MSC-based therapies in T1D,and to provide support for the clinical application of MSC in diabetes treatment.METHODS A conventional streptozotocin-induced T1D mouse model was established,and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected.The morphological and functional changes in the pancreas,liver,kidney,and spleen were analyzed by routine histological and immunohistochemical examinations.Changes in the serum cytokine levels in the model mice were assessed by protein arrays.The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot.RESULTS MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice.Immunofluorescence analysis revealed that the numbers of insulin+and CD31+cells in the pancreas were significantly increased in MSC-treated mice compared with control mice.Subsequent western blot analysis also showed that vascular endothelial growth factor(VEGF),Bcl2,Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice.Additionally,protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferonγand tumor necrosis factorαand upre
基金Supported by the National Council of Science and Technology of Mexico(CONACYT),No.790971(to Hernández-Melchor D),and No.781208 to(to Palafox-Gómez C).
文摘BACKGROUND Polycystic ovary syndrome(PCOS)is an endocrine disease that combines metabolic,reproductive,and psychological dysfunctions.Ovulation disorders and impaired endometrial receptivity in PCOS can cause infertility.Insulin resistance(IR)is a pathological state of inadequate response to insulin that affects reproduction in PCOS,as damage caused by IR at the endometrial level becomes an obstacle for embryo implantation.Reversing IR resulted in spontaneous pregnancies in PCOS patients,indicating that metabolic corrections improve endometrial dysfunctions.Mesenchymal stem-cell treatment has also corrected endometrial quality and lead to pregnancies in patients with Asherman’s syndrome.We propose a combination of nutritional intervention with the surgical placement of stem cells to improve endometrial quality to achieve pregnancy in a PCOS patient undergoing in vitro fertilization(IVF)treatment.CASE SUMMARY After two failed IVF cycles,a metabolic intervention,consisting of a ketogenic diet with daily consumption of 50 g of carbohydrates(CH),was indicated until pregnancy.Metabolic Syndrome was assessed using the Harmonizing Definition(3 of 5 pathologies:Central obesity,hypertension,hyperglycemia,hypertriglyceridemia,and dyslipidemia),and the Homeostatic Model Assessment of IR(HOMA-IR)was used to measure the level of IR.Once IR improved,endometrial quality improved.However,two day 5-thawed embryos(euploid,donated oocyte–partner's sperm)failed to implant,suggesting endometrial quality improvement was insufficient.Therefore,transmyometrial implantation of mesenchymal stem cells from the stromal vascular fraction of adipose tissue was performed to enrich the endometrial stem cell niche.Minimal endometrial mean thickness for embryo transfer(6.9 mm)was achieved three months after stem cell treatment and continuous dietary control of IR.Two euploid-day 5-thawed embryos(donated oocyte–partner's sperm)were transferred,and embryo implantation was confirmed on day 14 byβ-hCG serum levels.Currently,a 37 wk baby girl i
基金funded by the National Natural Science Foundation of China(81473721,81273789)。
文摘Background: Rhizoma drynariae is a traditional Chinese medicine used in orthopedics and traumatology, but its effect on endometrial receptivity remains unknown. Aims and Objectives: To observe effect of Rhizoma drynariae and its main components on endometrial receptivity in a mus model of dysfunctional embryo implantation. Materials and Methods: Mus models were established by the Gn RHa+HMG+HCG method. Normal mus receiving saline were used as controls and the remaining six groups were: model receiving saline, progynova, aspirin, Rhizoma drynariae, osteopractic total flavone, and naringin. Pinopodes in uterine endometrium were examined by scanning electron microscopy. Stem cell factor(SCF) m RNA expressions was determined by real-time RT-PCR, and estrogen receptor α(ERα), progesterone receptor(PR) by immunohistochemistry. Results: In the model group, surface morphology of endometrium was heterogeneous, without obvious pinopodes. In the Rhizoma drynaria and progynova groups, pinopodes were abundant. Compared with the blank group, model group had lower levels of SCF(-47%), ERα(-63%) and PR(-50%)(all P<0.05). In comparison, Rhizoma drynariae group had higher levels of SCF(+73%), ERα(+118%) and PR(+101%)(all P<0.01). The individual main components of Rhizoma drynariae had variable efficacy. Conclusion: Rhizoma drynariae could improve endometrial receptivity of mouse models of dysfunctional embryo implantation as shown by increased numbers of pinopodes and higher levers of SCF, ERα, PR compared with the model group.
