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Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model.

ABSTRACT: The incidence of premature ovarian failure (POF), also known as ovarian insufficiency, has been increasing in recent years. Although some treatments are currently available, improved treatment strategies are urgently required. Many researchers have reported that human endometrial stem cells (HuMenSCs), which exhibit stem/progenitor cell properties in vitro repaired damaged cells in vivo. Thus, we aimed to determine whether HuMenSCs can serve as cell therapy tools and be used for the treatment of POF. After treating with cyclophosphamide, on the first estrus period (we predicted mouse estrus cycle was generally 5 days), HuMenSCs were injected into a cyclophosphamide-induced mouse model of POF. The results revealed that the HuMenSCs could survive within POF mouse ovaries for at least 14 days in vivo; further, ovaries of the HuMenSCs-transplanted group expressed higher levels of ovarian markers [AMH, inhibin ?/?, and follicle-stimulating hormone receptor (FSHR)], and the proliferative marker Ki67. In addition, the ovarian weight, plasma E2 level, and the number of normal follicles increased over time in the HuMenSC group compared with the control group. Further, microarray analysis of cDNA expression patterns revealed that, after HuMenSC transplantation, the gene mRNA expression patterns in the ovarian cells following stimulation of the host ovarian niche became increasingly similar to those observed in human ovarian tissue compared with the pretransplantation mRNA expression pattern in HuMenSCs. Hence, we can safely conclude that the mesenchymal stem cell properties and in vivo survival of HuMenSCs make them ideal seed cells for stem cell transplantation in the treatment of POF.

SUBMITTER: Liu T

PROVIDER: S-EPMC4066227 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model.

Liu Te T Huang Yongyi Y Zhang Jian J Qin Wenxing W Chi Huiying H Chen Jiulin J Yu Zhihua Z Chen Chuan C

Stem cells and development 20140425 13

The incidence of premature ovarian failure (POF), also known as ovarian insufficiency, has been increasing in recent years. Although some treatments are currently available, improved treatment strategies are urgently required. Many researchers have reported that human endometrial stem cells (HuMenSCs), which exhibit stem/progenitor cell properties in vitro repaired damaged cells in vivo. Thus, we aimed to determine whether HuMenSCs can serve as cell therapy tools and be used for the treatment of ...[more]

PMID: 24593672

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Project description:BackgroundThere exists a dramatic rise in liver failure and numerous patients undergo liver transplant for life-saving reasons annually. Introducing alternatives to allo-graft transplantation is necessary due to present limitations. Recently, a noninvasive stem cell population from Menstrual blood-derived Stem Cells (MenSCs) has been identified. There is an increasing interest in the application of MenSCs in tissue engineering; however, the fact that these gender-specific stem cells are safe for use in male sex is still not well defined.MethodsIn this research, a model of acute liver failure was created in male and female immunocompetent Balb-C mice through intraperitoneal injection of Carbon tetrachlo-ride (CCl4 ) and MenSCs were transplanted intravenously 48 hrs after induction of liver injury to evaluate their therapeutic potential. All mice were sacrificed on days 1, 7, and 30 post-transplantation to examine biochemical and molecular markers and pathological appearances.ResultsResults showed the liver engraftment of MenSCs by immunofluorescence staining using anti-human mitochondrial antibody in both male and female treated groups. The restoration of serum markers of liver injury, aspartate aminotransferase and ala-nine aminotransferase, as well as expression levels of liver-specific genes, tyrosine aminotransferase and cholesterol 7 alpha-hydroxylase, were more significant in the female treated group compared with the male treated group on day 7 (p<0.05); however, after 30 days, there were no significant differences. Furthermore, hematoxylin and eosin and periodic acid-Schiff staining of liver sections demonstrated the considerable liver regeneration post cell therapy in both groups. Notably, data has shown that MenSCs could engraft into injured liver tissues and result in the same effect in the regeneration of liver function in both genders.ConclusionResults of this study introduce MenSCs therapy as an attractive alternative approach for liver repairing and regeneration which has no gender constraints.

Project description:BackgroundPremature ovarian insufficiency (POI) is one of the major causes of infertility. We previously demonstrated that transplantation of menstrual blood-derived stromal cells (MenSCs) effectively improved ovarian function in a murine model of POI. Recent studies indicated that mesenchymal stem cell-derived exosomes were important components in tissue repair. In this study, we investigated the therapeutic effects of MenSCs-derived exosomes (MenSCs-Exos) in a rat model of POI and its mechanism in restoring ovulation.MethodsOvaries of 4.5-day-old Sprague Dawley rats (SD rats) were cultured in vitro to evaluate the effects of MenSCs-Exos exposure on early follicle development. Furthermore, POI in rats was induced by intraperitoneal administration of 4-vinylcyclohexene diepoxide (VCD). Forty-eight POI rats were randomly assigned to four groups, each receiving a different treatment: PBS, MenSCs, MenSCs-Exos, and Exo-free culture supernatant of MenSCs. Estrous cyclicity, ovarian morphology, follicle dynamics, serum hormones, pregnancy outcomes, and molecular changes were investigated.ResultsExposure to MenSCs-Exos promoted the proliferation of granulosa cells in primordial and primary follicles in vitro and increased the expression of early follicle markers Deleted In Azoospermia Like (DAZL) and Forkhead Box L2 (FOXL2) while inhibiting follicle apoptosis. In vivo, MenSCs-Exos transplantation effectively promoted follicle development in the rat model of POI and restored the estrous cyclicity and serum sex hormone levels, followed by improving the live birth outcome. In addition, transplantation of MenSCs-Exos regulated the composition of the ovarian extracellular matrix and accelerated the recruitment of dormant follicles in the ovarian cortex and increased proliferation of granulosa cells in these follicles.ConclusionMenSCs-Exos markedly promoted follicle development in vitro and in vivo and restored fertility in POI rats, suggesting a restorative effect on ovarian functions. The therapeutic effect of MenSCs-Exos transplantation was sustainable, consistent with that of MenSCs transplantation. Our results suggested that MenSCs-Exos transplantation may be a promising cell-free bioresource in the treatment of POI.

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Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model.

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Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model.

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