Table 1.

Summary of recently reported preclinical trials using stem cell therapy to treat female infertility

Author, yr (Ref)	Types of models	Source of stem cells	Time of administration	Dose	Delivery route	Efficacy	Important findings
Xie et al. , 2019 (35)	PCOS in C57BL/6 mice was induced with DHEA	hUC-MScs	21 days after the modeling	(2 $\times$ 106 passage 4 hUC-MSCs suspended in 0.2 ml normal saline	Tail vein injection	By inhibiting local (ovaries and uterus) and systemic inflammatory responses, hUC-MSC treatment effectively improved the pathological changes and function of PCOS in mice	A mouse model of DHEA-induced PCOS was alleviated by MScs by inhibiting inflammation
Kalhori et al. , 2018 (45)	NMRI mice PCOS was induced through daily subcutaneous injections of testosterone enanthate dissolved in sesame oil	BM-MSCs	At 1 ${}^{\text{st}}$ and 14 ${}^{\text{th}}$ day after experimental induction of PCOS	(106 MSCs/animal)	Injected into the mice through the tail vein	The number of oocytes increased significantly as folliculogenesis increased whereas the number of primary and preantral follicles decreased significantly	Polycystic ovaries in mice injected with BM-MSCs showed improved folliculogenesis, oocyte quality and endocrine function due to their antioxidant, anti-inflammatory and anti-apoptotic properties
Jafarzadeh et al. , 2018 (46)	PCOS, 21-day-old female NMRI mice received daily subcutaneous injections of 6 mg/100 g bodyweight dehydroepiandrosterone	hBM-MSC derived CM	Condition medium was exposed to oocytes at the GV stage	The cells in the third passage were seeded at a density of 1 $\times$ 104 cells/cm2. Then, the CM was concentrated 10 times (10 $\times$ ) by centrifugation	Condition medium was exposed to oocytes at the GV stage	hBM-MSC-CM improved the oocyte -IVM, cytoplasmic maturation, fertilization and early embryo development rates	This study suggest that the cell-free therapeutic strategy can be efctive in the treatment of PCOS
Chugh et al. , 2021 (47)	For in vitro experiment, conditioned media from BM-hMSC was exposed to androgen-producing H293R cells and analyzed androgen-producing gene expression. For in vivo experiment, BM-hMSC were implanted into a letrozole-induced PCOS mouse model	hBM-MSCs	5 wk after modeling	5.0 $\times$ 105 cells per ovary resuspended in 10 μl PBS	Intra-ovarian injection of BM-hMSC via laparotomy	This research indicated the efficacy of intra-ovarian injection of secretome of BM-hMSC that effectively improved the PCOS-related symptoms	BM-hMSC or its secretome potentially reversed the inflammation caused by PCOS-via IL-10 secretion
PCOS: Polycystic ovary syndrome, DHEA: Dehydroepiandrosterone, hUC-MScs: Human umbilical cord-mesenchymal stem cells, BM-MSCs: Bone marrow mesenchymal stem cells, hBM-MSC: Human bone marrow mesenchymal stromal cells, CM: Condition medium, GV: Germinal vesicle, IVM: In vitro maturation, PBS: Phosphate buffered saline, IL-10: Interleukin-10