Published online Aug 26, 2020. doi: 10.4252/wjsc.v12.i8.857
Peer-review started: February 22, 2020
First decision: April 29, 2020
Revised: June 1, 2020
Accepted: July 18, 2020
Article in press: July 18, 2020
Published online: August 26, 2020
Premature ovarian failure (POF) is characterized by amenorrhea, hypoestrogenemia, high gonadotropins and infertility in women under 40-years-old. Previous reports demonstrated that various tissue-specific stem cells could restore ovarian function and folliculogenesis in chemotherapy-induced POF mice.
Human embryonic stem cell-derived MSC (ES-MSC) have advantages, such as higher proliferation, more potent anti-inflammatory properties and lack of obstacles of harvesting tissue-specific MSCs that make them attractive candidates for restoring fertility in patients with POF.
The aim of this study was to evaluate the therapeutic efficacy of ES-MSCs in a model of chemotherapy-induced POF.
In this study, we initially established a mouse POF model by administration of cyclophosphamide and busulfan, then we transplanted ES-MSCs and bone marrow-derived MSC (BM-MSC) into a mouse model of POF to investigate the role of these cells and mechanisms of action for improvement of POF.
The POF model established by the 100 mg/kg dose of cyclophosphamide showed significant decreases in body weight, follicle count and estradiol level but had an increased follicle-stimulating hormone level. ES-MSC and/or BM-MSC transplantation significantly improved body weight, follicle count, hormone secretion, survival rate and reproductive function in POF mice. Gene expression and Western blot analysis, terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labelling assay and immunohistochemistry indicated that the ES-MSCs or BM-MSCs reduced apoptosis in the follicles and restored fertility in chemotherapy-induced POF mice. The results of this study indicated that the effects of ES-MSCs and BM-MSCs in restoring ovarian function appear via the paracrine mechanisms of cytokines.
Our findings demonstrated that human ES-MSCs, similar to BM-MSCs, improved ovarian function and restored fertility in a mouse POF model.
Our present study results suggest that human ES-MSCs could be a promising source for stem cell therapy in individuals with POF.