Human Amniotic Epithelial Stem Cells Alleviate Autoimmune Premature Ovarian Insufficiency in Mice by Targeting Granulosa Cells via AKT/ERK Pathways.
Xiaohang YeYifeng LinYanyun YingXuezhi ShenFeida NiFeixia WangJianpeng ChenWei ZhaoXiaoming YuDan ZhangYifeng LiuPublished in: Stem cell reviews and reports (2024)
Autoimmune factors play an important role in premature ovarian insufficiency (POI). Human amniotic epithelial stem cells (hAESCs) have recently shown promising treatment effects on chemotherapy-induced POI. However, the therapeutic efficacy and underlying mechanisms of hAESCs in autoimmune POI remain to be investigated. In this study, we showed for the first time that intravenous transplantation of hAESCs could reside in the ovary of zona pellucida 3 peptide (pZP3) induced autoimmune POI mice model for at least 4 weeks. hAESCs could improve ovarian function and fertility, alleviate inflammation and reduce apoptosis of granulosa cells (GCs) in autoimmune POI mice. The transcriptome analysis of mice ovaries and in vitro co-cultivation experiments suggest that activation of the AKT and ERK pathways may be the key mechanism in the therapeutic effect of hAESCs. Our work provides the theoretical and experimental foundation for optimizing the administration of hAESCs, as well as the clinical application of hAESCs in autoimmune POI patients.
Keyphrases
- stem cells
- signaling pathway
- multiple sclerosis
- cell cycle arrest
- induced apoptosis
- high fat diet induced
- drug induced
- cell proliferation
- pi k akt
- endothelial cells
- oxidative stress
- endoplasmic reticulum stress
- cell death
- end stage renal disease
- newly diagnosed
- chemotherapy induced
- cell therapy
- dna methylation
- type diabetes
- insulin resistance
- skeletal muscle
- metabolic syndrome
- single cell
- genome wide
- wild type
- pluripotent stem cells
- low dose
- high speed
- combination therapy