Recovery of ovarian function by human embryonic stem cell-derived mesenchymal stem cells in cisplatin-induced premature ovarian failure in mice.
Stem Cell Res Ther
; 11(1): 255, 2020 06 26.
Article
en En
| MEDLINE
| ID: mdl-32586410
BACKGROUND: Clinical use of mesenchymal stem cells (MSCs) requires a uniform cell population, and their harvesting is invasive and produces a limited number of cells. Human embryonic stem cell-derived MSCs (hESC-MSCs) can differentiate into three germ layers and possess immunosuppressive effects in vitro. Anticancer treatment is a well-known risk factor for premature ovarian failure (POF). In this study, we investigated the effect of hESC-MSC on recovery of ovarian function in cisplatin-induced POF in mice. METHODS: Female mice received intraperitoneal cisplatin for 10 days. On day 12, CHA15-derived hESC-MSCs were transplanted into the mice by tail vein injection. An injection of PBS served as the negative control. Ovaries were removed 28 days after transplantation for assessment of ovarian histology, immunostaining, and fertility testing by superovulation and in vitro fertilization. hESC-MSC transplantation into mice with cisplatin-induced damage restored body weight and ovary size. RESULTS: Mean primary and primordial follicle counts in the hESC-MSC group were significantly improved compared to the PBS group (P < 0.05), and counts of zona pellucida remnants, an apoptotic sign in ovarian follicles, were significantly reduced (P < 0.05). TUNEL assays and cleaved PARP immunostaining indicated apoptosis, which led to loss of ovarian stromal cells in negative control mice, while Ki-67 was higher in the hESC-MSC group and in non-cisplatin-treated controls than in the PBS group. Ovulation was reduced in the PBS group but recovered significantly in the hESC-MSC group. Rates of blastocyst formation from ovulated eggs and live births per mouse also recovered significantly in the hESC-MSC group. CONCLUSIONS: hESC-MSC restored structure and function in the cisplatin-damaged ovary. Our study provides new insights into the great clinical potential of human hESC-MSC in treating POF.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Insuficiencia Ovárica Primaria
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Trasplante de Células Madre Mesenquimatosas
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Células Madre Mesenquimatosas
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Células Madre Embrionarias Humanas
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Stem Cell Res Ther
Año:
2020
Tipo del documento:
Article
País de afiliación:
Corea del Sur
Pais de publicación:
Reino Unido