Human Umbilical Cord Mesenchymal Stem Cells Improve Ovarian Function in Chemotherapy-Induced Premature Ovarian Failure Mice Through Inhibiting Apoptosis and Inflammation via a Paracrine Mechanism

2021 ◽  
Author(s):  
Taoran Deng ◽  
Jing He ◽  
Qingyun Yao ◽  
Linjing Wu ◽  
Liru Xue ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Premature Ovarian Failure ◽  
Ovarian Function ◽  
Ovarian Failure ◽  
Human Umbilical Cord ◽  
Apoptosis And Inflammation

scholarly journals Effects of single transplantation and multiple transplantation of human umbilical cord mesenchymal stem cells on the recovery of ovarian function in the treatment of premature ovarian failure in mice

2021 ◽  
Author(s):  
Xiaodan Lv ◽  
Chunyi Guan ◽  
Ying Li ◽  
Xing Su ◽  
lu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Real Time ◽  
Umbilical Cord ◽  
Premature Ovarian Failure ◽  
Real Time Pcr ◽  
Ovarian Function ◽  
Follicle Stimulating Hormone ◽  
Ovarian Failure ◽  
Human Umbilical Cord

Abstract BackgroundAt present, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in a variety of diseases including POI, but the method and dosage of hUC-MSCs to treat POI are not clear. This study aims to explore the treatment options of hUC-MSCs for POF by comparing single injection and multiple injections of hUC-MSCs on the ovarian function repair of POF caused by chemotherapy drugs.MethodsFemale mice were injected intraperitoneally with 30 mg/kg of busulfan and 120 mg/kg of cyclophosphamide to induce POF. In the single hUC-MSCs injection group, 7 days after the mice were injected with cyclophosphamide and busulfan, hUC-MSCs were transplanted into these mice. In the multiple injection group, hUC-MSCs were transplanted 7 days, 14 days and 21 days after the mice were injected with cyclophosphamide and busulfan. We evaluated ovarian morphology, fertility, follicle stimulating hormone and estradiol concentration, and follicle count, evaluated POF model and cell transplantation. In addition, real-time PCR, immunohistochemistry, miRNA chip and mRNA chip are used to evaluate the effect of cell therapy.ResultsCompared with the POF group, the ovarian size and primordial follicle count in the hUC-MSC group were significantly improved, and the fertility was also significantly improved. Immunohistochemistry showed that compared with the POF group, the anti-Mullerian hormone and Ki-67 in the ovary of the hUC-MSC group increased significantly, and ovulation was significantly restored. Real-time PCR showed that the expression of follicle stimulating hormone receptor, inhibin and inhibin in the hUC-MSCs group was significantly restored compared with the POF group. The results of mRNA and miRNA chips also showed that hUC-MSC restored ovarian function at the gene level. long-term treatment effect shows that the multiple transplantation hUC-MSCs group is better than the single transplantation hUC-MSCs group. 60 days after the mice were injected with cyclophosphamide and busulfan, the organ coefficient of multiple transplantation of hUC-MSCs increased compared with the POF group, the number of primary follicles increased, and hormone secretion increased. ConclusionThe results show that multiple trasplantation of hUC-MSCs can promote the recovery of ovarian function in POF mice more than a single transplantation. This study provides a basis for the therapeutic dose and therapeutic effect of hUC-MSCs on POF.

scholarly journals Human Umbilical Cord Mesenchymal Stem Cells Therapy in Cyclophosphamide-Induced Premature Ovarian Failure Rat Model

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Dan Song ◽  
Yun Zhong ◽  
Chunfeng Qian ◽  
Qinyan Zou ◽  
Jian Ou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Rat Model ◽  
Premature Ovarian Failure ◽  
Ovarian Function ◽  
Hormone Secretion ◽  
Ovarian Failure ◽  
Human Umbilical Cord ◽  
Ovarian Cells

Premature ovarian failure (POF) is one of the most common causes of infertility in women. In our present study, we established cyclophosphamide- (CTX-) induced POF rat model and elucidated its effect on ovarian function. We detected the serum estrogen, follicle stimulating hormone, and anti-Müllerian hormone of mice models by ELISA and evaluated their folliculogenesis by histopathology examination. Our study revealed that CTX administration could severely disturb hormone secretion and influence folliculogenesis in rat. This study also detected ovarian cells apoptosis by deoxy-UTP-digoxigenin nick end labeling (TUNEL) and demonstrated marked ovarian cells apoptosis in rat models following CTX administration. In order to explore the potential of human umbilical cord mesenchymal stem cells (UCMSCs) in POF treatment, the above indexes were used to evaluate ovarian function. We found that human UCMSCs transplantation recovered disturbed hormone secretion and folliculogenesis in POF rat, in addition to reduced ovarian cell apoptosis. We also tracked transplanted UCMSCs in ovaries by fluorescencein situhybridization (FISH). The results manifested that the transplanted human UCMSCs could reside in ovarian tissues and could survive for a comparatively long time without obvious proliferation. Our present study provides new insights into the great clinical potential of human UCMSCs in POF treatment.

scholarly journals Effects of Single Transplantation and Multiple Transplantation of Human Umbilical Cord Mesenchymal Stem Cells on the Recovery of Ovarian Function in the Treatment of Premature Ovarian Failure in Mice

2020 ◽  
Author(s):  
Xiaodan Lv ◽  
Chunyi Guan ◽  
Ying Li ◽  
Xing Su ◽  
lu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Premature Ovarian Failure ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Ovarian Failure ◽  
Mouse Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Umbilical Cord

Abstract Background: Previous studies have reported that transplantation of mesenchymal stem cells (MSCs) from many human tissues can improve ovarian dysfunction. However, the therapeutic effects of single injection of MSCs and multiple injections of MSCs on premature ovarian failure (POF) have not been reported yet. In this study, we used long-term follow-up to study the effect of human umbilical cord mesenchymal stem cell (hUC-MSCs) on the functional recovery of mouse POF models. Methods: In this study, we used a mouse model of premature ovarian failure induced by the combination of 120mg/kg cyclophosphamide and 30mg/kg busulfan. Enzyme-linked immunosorbent assay (ELISA) was used to detect estradiol (E2) and follicle stimulating hormone (FSH) levels in mouse serum. Evaluate ovarian function by counting follicles, ovarian weight, number of proliferating cells, anti-Mullerian hormone (AMH) and oocytes. Results: Our study shows that hUC-MSCs have obvious therapeutic effect for the POF mice model, and treatment effect of multiple transplantation is better than single transplantation. Mesenchymal stem cells were detected in follicular granulosa cells with tracer of the ovarian tissue freezing slice, which show hUC-MSCs to selectively migration and stay in damaged tissues. Genome Array screened a number of differentially expressed genes, the hUC-MSCs can change the level of expression of certain genes in the ovarian tissue, thus affecting ovarian function, and laid the foundation for us to further explore the mechanism of hUC-MSCs treatment of premature ovarian failure. Conclusion: This study demonstrated that hUC-MSCs transplantation significantly restored ovarian function after chemotherapy-induced damage.

scholarly journals Effects of single and multiple transplantations of human umbilical cord mesenchymal stem cells on the recovery of ovarian function in the treatment of premature ovarian failure in mice

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaodan Lv ◽  
Chunyi Guan ◽  
Ying Li ◽  
Xing Su ◽  
Lu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Umbilical Cord ◽  
Premature Ovarian Failure ◽  
Ovarian Function ◽  
Ovarian Failure ◽  
Human Umbilical Cord ◽  
Injection Group ◽  
Ovarian Morphology

Abstract Background Currently, there is no effective treatment for premature ovarian failure (POF), and stem cell therapy is considered the most promising treatment. Human umbilical cord blood mesenchymal stem cells (hUC-MSCs) have shown good regenerative ability in various diseases, including POF; however, their underlying mechanism and dosage for POF treatment remain unclear. This study aimed to compare the effect of single and multiple injections of hUC-MSCs on ovarian function repair in chemotherapy-induced POF. Methods Female mice were intraperitoneally injected with 30 mg/kg busulfan and 120 mg/kg cyclophosphamide (CTX) to induce POF. In the single hUC-MSC injection group, hUC-MSCs were transplanted into mice D7 after CTX and busulfan administration, while in the multiple injection group, hUC-MSCs were transplanted on D7, D14, and D21 after CTX and busulfan administration. We evaluated the ovarian morphology, fertility, follicle-stimulating hormone and estradiol concentrations, follicle count, POF model, and cell transplantation results. In addition, real-time polymerase chain reaction, immunohistochemistry, and miRNA and mRNA chips were used to evaluate the effect of the cell therapy. Results Ovary size, number of follicle at all developmental stages, and fertility were significantly reduced in the POF group compared with the control. Under hUC-MSC treatment, the ovarian morphology and follicle count were significantly restored, and fertility was significantly increased. By comparing the single and multiple hUC-MSC injection groups, we found that the anti-Müllerian hormone and Ki-67 levels were significantly increased in the multiple hUC-MSC group on D60 after chemotherapy. The expression of stimulating hormone receptors, inhibin α, and inhibin β was significantly restored, and the therapeutic effect was superior to that of the single hUC-MSC injection group. Conclusion These results indicate that hUC-MSCs can restore the structure of injured ovarian tissue and its function in chemotherapy-induced POF mice and ameliorate fertility. Multiple hUC-MSC transplantations have a better effect on the recovery of ovarian function than single hUC-MSC transplantation in POF.

scholarly journals The Therapeutic Potential of Umbilical Cord Mesenchymal Stem Cells in Mice Premature Ovarian Failure

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Shufang Wang ◽  
Ling Yu ◽  
Min Sun ◽  
Sha Mu ◽  
Changyong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Granulosa Cells ◽  
Premature Ovarian Failure ◽  
Ovarian Function ◽  
Treated Group ◽  
Ovarian Failure ◽  
Control Group ◽  
Wild Type

Mesenchymal stem cells, which are poorly immunogenic and have potent immunosuppressive activities, have emerged as promising cellular therapeutics for the treatment of several diseases. Mesenchymal-like cells derived from Wharton’s Jelly, called umbilical cord matrix stem cells (UCMSCs), reportedly secrete a variety of cytokines and growth factors, acting as trophic suppliers. Here, we used UCMSCs to treat premature ovarian failure (POF). Ovarian function was evaluated by ovulation and the number of follicles. Apoptosis of the granulosa cells (GC) was analyzed by TUNEL staining. We found that after transplantation of the UCMSCs, apoptosis of cumulus cells in the ovarian damage model was reduced and the function of the ovary had been recovered. The sex hormone level was significantly elevated in mice treated with UCMSCs. The number of follicles in the treated group was higher than in the control group. Our results demonstrate that UCMSCs can effectively restore ovary functionality and reduce apoptosis of granulosa cells. We compared the RNA expression of the UCMSCs treated group with the POF model and wild-type control group and found that the UCMSC group is most similar to the wild-type group. Our experiments provide new information regarding the treatment of ovarian function failure.

scholarly journals Transplantation of human umbilical cord mesenchymal stem cells to treat premature ovarian failure

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Oldouz Shareghi-oskoue ◽  
Leili Aghebati-Maleki ◽  
Mehdi Yousefi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Umbilical Cord ◽  
Premature Ovarian Failure ◽  
Treatment Strategies ◽  
Ovarian Failure ◽  
Human Umbilical Cord ◽  
Stem Cell Treatment

AbstractAs one of the problems and diseases for women before 40 years, premature ovarian failure (POF) could be characterized by amenorrhea, low estrogen levels, infertility, high gonadotropin levels, and lack of mature follicles. Causes of the disease involve some genetic disorders, autoimmunity diseases, and environmental factors. Various approaches have been employed to treat POF, however with limited success. Today, stem cells are used to treat POF, since they have the potential to self-repair and regenerate, and are effective in treating ovarian failure and infertility. As mesenchymal stem cell (MSC) could simultaneously activate several mechanisms, many researchers consider MSC transplantation to be the best and most effective approach in cell therapy. A good source for mesenchymal stem cells is human umbilical cord (HUCMSC). Animal models with cyclophosphamide are required for stem cell treatment and performance of HUCMSC transplantation. Stem cell therapy could indicate the levels of ovarian markers and follicle-stimulating hormone receptor. It also increases ovarian weight, plasma E2 levels, and the amount of standard follicles. Herein, the causes of POF, effective treatment strategies, and the effect of HUCMSC transplantation for the treatment of premature ovarian failure are reviewed. Many studies have been conducted in this field, and the results have shown that stem cell treatment is an effective approach to treat infertility.

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