Matrigel/umbilical cord-derived mesenchymal stem cells promote granulosa cell proliferation and ovarian vascularization in a mouse model of premature ovarian failure

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.

Download Full-text

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

BioMed Research International ◽

10.1155/2016/2517514 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 21

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.

Download Full-text

Transplantation of umbilical cord–derived mesenchymal stem cells on a collagen scaffold improves ovarian function in a premature ovarian failure model of mice

In Vitro Cellular & Developmental Biology - Animal ◽

10.1007/s11626-019-00337-4 ◽

2019 ◽

Vol 55 (4) ◽

pp. 302-311 ◽

Cited By ~ 4

Author(s):

Yanjun Yang ◽

Lei Lei ◽

Shanshan Wang ◽

Xiaoqiang Sheng ◽

Guijun Yan ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Premature Ovarian Failure ◽

Ovarian Function ◽

Collagen Scaffold ◽

Ovarian Failure ◽

Failure Model

Download Full-text

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

BioMed Research International ◽

10.1155/2013/690491 ◽

2013 ◽

Vol 2013 ◽

pp. 1-12 ◽

Cited By ~ 25

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.

Download Full-text

Umbilical cord blood mesenchymal stem cells as an infertility treatment for chemotherapy induced premature ovarian failure

Fertility and Sterility ◽

10.1016/j.fertnstert.2016.07.382 ◽

2016 ◽

Vol 106 (3) ◽

pp. e128 ◽

Cited By ~ 2

Author(s):

S.A. Mohamed ◽

S.M. Shalaby ◽

S. Brakta ◽

L. Stone ◽

M. Ellakany ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cord Blood ◽

Umbilical Cord ◽

Umbilical Cord Blood ◽

Premature Ovarian Failure ◽

Infertility Treatment ◽

Ovarian Failure

Download Full-text

Effects of umbilical cord mesenchymal stem cells on expression of CYR61, FSH and AMH in mice with premature ovarian failure

Cellular and Molecular Biology ◽

10.14715/cmb/2021.67.5.41 ◽

2022 ◽

Vol 67 (4) ◽

pp. 358-366

Author(s):

He Jie ◽

Wang Jinxiang ◽

Li Ye ◽

Zhao Jing ◽

Zhu Xiangqing ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Protein Expression ◽

Umbilical Cord ◽

Premature Ovarian Failure ◽

Caspase 3 ◽

Ovarian Failure ◽

Tissue Growth ◽

Mesenchymal Stem Cell Transplantation ◽

The Difference

The aim of this study was to objective to investigate the effects of umbilical cord mesenchymal stem cells on the expression of CYR61, FSH and AMH in mice with premature ovarian failure. For this purpose, thirty SPF female SD mice were selected as the research object, 10 of which were control group, namely group α, and 20 mice with premature ovarian failure model were established by cyclophosphamide. The mice were divided into model group, namely β group and the umbilical cord mesenchymal stem cell transplantation group (γ group), with 10 mice in each group. ELSA method was used to determine the levels of follicle-stimulating hormone (FSH), Luteinizing hormone (LH), estradiol (Estradiol) in serum. The changes of E2, Antimullerian hormone (AMH) and cysteine-rich protein 61 in ovarian tissues were determined by the protein imprinting method. Connective tissue growth factor (CTGF) and caspase-3 protein expression. Results showed that in fertility rate, γ group > α group > β group, the difference was statistically significant (P<0.05), in litter size, α group > γ group > β group, the difference was statistically significant (P<0.05). The levels of serum E2 and AMH in α group > γ group > β group, and the levels of serum FSH and LH in β group > γ group > α group were statistically significant (P<0.05). The growth follicles were α group > γ group > β group, and the atresia follicles were β group > γ group > α group, and there was a statistical difference among all groups (P<0.05). There was no difference in luteal number among the three groups (P>0.05). In terms of CYR61 and CTGF protein expression, α group > γ group > β group, and in terms of caspase-3, β group > γ group > α group had statistical significance (P<0.05). It is concluded that intervention with umbilical cord mesenchymal stem cells can significantly improve the expression levels of CYR61 and AMH, reduce the level of FSH, promote cell survival, improve the reproductive quality of mice, and restore the physiological function of the ovary. It is feasible to treat premature ovarian failure with umbilical cord mesenchymal stem cells.

Download Full-text