Research Progress of Stem Cell Therapy for Premature Ovarian Insufficiency.
- 1Department of Gynaecology and Obstetrics, Qinghai Red Cross Hospital, Xining, Qinghai, 810000, People's Republic of China.
- 2Graduate School of Qinghai University, Xining, Qinghai, 810007, People's Republic of China.
Abstract
Premature ovarian insufficiency (POI) is a heterogeneous reproductive and endocrine disorder characterized by impaired ovarian function before the age of 40 years. Conventional management, particularly hormone therapy, addresses hypoestrogenic symptoms and long-term health risks but does not reliably restore endogenous ovarian activity or fertility. Stem cell-based strategies have therefore attracted considerable interest because of their potential paracrine, immunomodulatory, anti-apoptotic, angiogenic, and microenvironment-remodeling effects. This review summarizes current evidence on stem cell sources, therapeutic mechanisms, preclinical models, clinical studies, extracellular vesicle-based approaches, biomaterials, gene-editing strategies, and translational challenges in POI. Particular emphasis is placed on the distinction between mechanistic and animal evidence, uncontrolled or pilot human studies, and controlled clinical evidence. Across preclinical models, mesenchymal stem cells (MSCs) frequently improve ovarian histology, hormone profiles, follicular parameters, and reproductive performance; however, these findings cannot be assumed to represent restoration of ovarian reserve or fertility in humans. Clinical evidence remains limited, heterogeneous, and predominantly derived from small non-randomized studies, with outcomes ranging from menstrual recovery and changes in AMH, FSH, estradiol, or antral follicle count to a small number of reported pregnancies. These surrogate changes should be distinguished from clinically meaningful endpoints such as ovulation, ongoing pregnancy, and live birth. Emerging approaches involving extracellular vesicles, biomaterials, and gene editing may improve cell retention or therapeutic potency, but most remain preclinical or early translational strategies. Overall, stem cell therapy should currently be regarded as an investigational approach for POI. Progress toward clinical translation will require standardized cell products, clearly defined dosing and administration routes, appropriate comparator groups, clinically meaningful reproductive endpoints, rigorous long-term safety surveillance, and adequately powered controlled trials.
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BibTeX
@article{zhang2026research,
title = {{Research Progress of Stem Cell Therapy for Premature Ovarian Insufficiency.}},
author = {Shuna Zhang and Fei Wang and Ruiqi Wang and Huilin Yang and Liehong Wang},
journal = {International journal of general medicine},
year = {2026},
month = oct,
doi = {10.2147/ijgm.s638363},
url = {https://europepmc.org/article/MED/42959858},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Research Progress of Stem Cell Therapy for Premature Ovarian Insufficiency.
AU - Shuna Zhang
AU - Fei Wang
AU - Ruiqi Wang
AU - Huilin Yang
AU - Liehong Wang
PY - 2026
DA - 2026/10/25
JO - International journal of general medicine
DO - 10.2147/ijgm.s638363
UR - https://europepmc.org/article/MED/42959858
AB - Premature ovarian insufficiency (POI) is a heterogeneous reproductive and endocrine disorder characterized by impaired ovarian function before the age of 40 years. Conventional management, particularly hormone therapy, addresses hypoestrogenic symptoms and long-term health risks but does not reliably restore endogenous ovarian activity or fertility. Stem cell-based strategies have therefore attracted considerable interest because of their potential paracrine, immunomodulatory, anti-apoptotic, angiogenic, and microenvironment-remodeling effects. This review summarizes current evidence on stem cell sources, therapeutic mechanisms, preclinical models, clinical studies, extracellular vesicle-based approaches, biomaterials, gene-editing strategies, and translational challenges in POI. Particular emphasis is placed on the distinction between mechanistic and animal evidence, uncontrolled or pilot human studies, and controlled clinical evidence. Across preclinical models, mesenchymal stem cells (MSCs) frequently improve ovarian histology, hormone profiles, follicular parameters, and reproductive performance; however, these findings cannot be assumed to represent restoration of ovarian reserve or fertility in humans. Clinical evidence remains limited, heterogeneous, and predominantly derived from small non-randomized studies, with outcomes ranging from menstrual recovery and changes in AMH, FSH, estradiol, or antral follicle count to a small number of reported pregnancies. These surrogate changes should be distinguished from clinically meaningful endpoints such as ovulation, ongoing pregnancy, and live birth. Emerging approaches involving extracellular vesicles, biomaterials, and gene editing may improve cell retention or therapeutic potency, but most remain preclinical or early translational strategies. Overall, stem cell therapy should currently be regarded as an investigational approach for POI. Progress toward clinical translation will require standardized cell products, clearly defined dosing and administration routes, appropriate comparator groups, clinically meaningful reproductive endpoints, rigorous long-term safety surveillance, and adequately powered controlled trials.
SN - 1178-7074
ER -