2. Academic Validation
  3. Human Amniotic Epithelial Stem Cells Alleviate Autoimmune Premature Ovarian Insufficiency in Mice by Targeting Granulosa Cells via AKT/ERK Pathways

Human Amniotic Epithelial Stem Cells Alleviate Autoimmune Premature Ovarian Insufficiency in Mice by Targeting Granulosa Cells via AKT/ERK Pathways

  • Stem Cell Rev Rep. 2024 Jun 4. doi: 10.1007/s12015-024-10745-z.
Xiaohang Ye 1,  Yifeng Lin # 1,  Yanyun Ying # 1,  Xuezhi Shen 1,  Feida Ni 1,  Feixia Wang 1,  Jianpeng Chen 1,  Wei Zhao 1,  Xiaoming Yu 1,  Dan Zhang 2 3,  Yifeng Liu 4 5
Affiliations

Affiliations

  • 1 Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Zhejiang, 310006, China.
  • 2 Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Zhejiang, 310006, China. zhangdan@zju.edu.cn.
  • 3 Zhejiang Provincial Clinical Research Center for Child Health, Hangzhou, 310006, China. zhangdan@zju.edu.cn.
  • 4 Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Zhejiang, 310006, China. zjulyf@zju.edu.cn.
  • 5 Zhejiang Provincial Clinical Research Center for Child Health, Hangzhou, 310006, China. zjulyf@zju.edu.cn.
  • # Contributed equally.
PMID: 38831179 DOI: 10.1007/s12015-024-10745-z
Abstract

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.

Keywords

AKT; Autoimmune premature ovarian insufficiency; ERK; Granulosa cells; Human amniotic epithelial stem cells.

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