Stem Cell-Based Therapeutic Strategies for Premature Ovarian Insufficiency and Infertility: A Focus on Aging

Abstract

Reproductive aging is on the rise globally and inseparable from the entire aging process. An extreme form of reproductive aging is premature ovarian insufficiency (POI), which to date has mostly been of idiopathic etiology, thus hampering further clinical applications and associated with enormous socioeconomic and personal costs. In the field of reproduction, the important functional role of inflammation-induced ovarian deterioration and therapeutic strategies to prevent ovarian aging and increase its function are current research hotspots. This review discusses the general pathophysiology and relative causes of POI and comprehensively describes the association between the aging features of POI and infertility. Next, various preclinical studies of stem cell therapies with potential for POI treatment and their molecular mechanisms are described, with particular emphasis on the use of human induced pluripotent stem cell (hiPSC) technology in the current scenario. Finally, the progress made in the development of hiPSC technology as a POI research tool for engineering more mature and functional organoids suitable as an alternative therapy to restore infertility provides new insights into therapeutic vulnerability, and perspectives on this exciting research on stem cells and the derived exosomes towards more effective POI diagnosis and treatment are also discussed.

The mechanism of adipose mesenchymal stem cells to stabilize the immune microenvironment of pelvic floor injury by regulating pyroptosis and promoting tissue repair

“…3 B, P < 0.001 ). The most recent theory state that free radicals, inflammation, and aging are intimately connected [ 26 ]. As a result, LPS-treated fibroblasts were stained with β-galactosidase, and the aging cells produced dark blue products.…”

Perspective Chapter: Ovarian Reproductive Aging and Rejuvenation Strategies

“…Additionally, FBS, PRP, PRP + FBS, or human serum albumin were cultured with the follicles from Mechanisms involved in stem cell-based therapies in POF. Adapted from [170].…”

Biological therapies for premature ovarian insufficiency: what is the evidence?

“…Exosomes (exos) are extracellular vesicles released, principally from mesenchymal stem cells (MSCs), ranging in size from 30 nm to 150 nm ( 58 ). By releasing non-coding RNA, mRNA, growth factors and proteins, exos are active in influencing cellular communication as well as the fate of recipient cells, via regulation of proliferation and apoptosis ( 14 , 59 – 62 ). In rodent models of POI, the administration of exos from various human MSCs, such as bone marrow-derived MSCs (BMSCs) ( 63 ), umbilical cord MSCs (UC-MSCs) ( 64 ), and adipose tissue-derived MSCs (ADSCs) ( 65 ), as well as from human embryonic stem cells (ESC) ( 66 ) and human pluripotent stem cell–mesenchymal stem cells (hiMSC) ( 67 ) is demonstrated to recover the oestrous cycle ( 63 ), to increase the hormone levels, the AMH level and the number of follicles ( 63 , 65 – 67 ), as well as to prevent follicular atresia ( 63 , 67 ) and to enhance the fertility rate by reducing the time of impregnation ( 64 ).…”

“…In conclusion, the available research data is encouraging and many authors and researchers now recognize exos treatment as a potential treatment for POI. Exos are considered as potentially safer than stem cells (SCs) due to lack of tumorigenicity, low immunogenicity, and no ethical concerns ( 62 ). However, in order to be considered for POI patients, their efficacy and safety needs to be assessed in human clinical trials.…”