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 α/β, 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.

The protective effects of human umbilical cord mesenchymal stem cells on damaged ovarian function: A comparative study

“…Evidence has shown that hUCMSCs have unique advantages compared to BMSCs (22), which make them a promising source of cells for treatment. According to previous studies, stem cells to treat ovarian injury are primarily administered via intravenous injection (IV) or in situ ovarian micro injection (MI) (23)(24)(25)(26). However, very few studies have examined suitable forms of hUCMSC therapy to delay ovarian aging.…”

Tripterygium glycosides induce premature ovarian failure in rats by promoting p53 phosphorylation and activating the serine/threonine kinase 11-p53-p21 signaling pathway

“…Premature ovarian failure (POF) is a typical pathological disease of the reproductive system in aging females (1)(2)(3)(4)(5). Patients with POF are <40 years old and commonly have the features of amenorrhea, hypoestrogenism and high levels of gonadotrophin (1)(2)(3)(4)(5).…”

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“…Las técnicas y fórmulas utilizadas están descritas en la bibliografía (20)(21)(22)(23)(24). Se tomaron entre 5 y 10 muestras de cada mezcla obtenida y se anotaron, según procediese, los valores correspondientes.…”

“…El concepto más valorado fue el ítem nº 4 "concepto de componente básico (células madre)" con una media de 4,63 puntos sobre un máximo de 5; lo que sin duda se debe a la importancia que, en el campo de la Ingeniería Tisular, tiene el concepto de célula madre como elemento inherente a esta ciencia y base esencial y fundamental de la misma (20)(21)(22). Por otro lado el ítem menor puntuado fue el nº 9 "concepto de biofabricación (bioimpresoras)" con una media de 3,13 sobre 5; ello se debe probablemente a su reciente aparición en el contexto de la ingeniería tisular y al poco conocimiento de dicho concepto por parte del alumnado, que considera el proceso de biofabricación menos relevante y más relacionado con aspectos tecnológicos que con aspectos propiamente biomédicos (23,24).…”

“…En modelos animales han resultado ser útiles en la insuficiencia ovárica [22], en el reemplazo de neuronas dopaminérgicas en enfermedad de Parkinson [21]; aumentaron el número de islotes beta-pancreáticos en el páncreas de ratones con diabetes tipo I [7], mejoran la enfermedad de Duchenne en ratones al diferenciarlas en tejido muscular esquelético [4], han sido utilizadas en ratones infartados donde fueron diferenciadas a cardiomiocitos con la consecuente mejora de la función cardiaca [4], administradas de forma local su eficacia ha sido demostrada en modelos animales para enfermedades inflamatorias crónicas como esclerosis múltiple [3], encefalomielitis autoinmune [4] y colitis ulcerosa [8].…”