Abstract
With the development of regenerative medicine, stem cells are being considered more frequently for the treatment of reproductive aging. Human umbilical cord mesenchymal stem cells have been reported to improve the reserve function of aging ovaries through their homing and paracrine effects. In this process, paracrine factors secreted by stem cells play an important role in ovarian recovery. Although the transplantation of human umbilical cord mesenchymal stem cells to improve ovarian function has been studied with great success in animal models of reproductive aging, their application in clinical research and therapy is still relatively rare. Therefore, this paper reviews the role of human umbilical cord mesenchymal stem cells in the treatment of reproductive aging and their related mechanisms, and it does so in order to provide a theoretical basis for further research and clinical treatment.
Highlights
Delaying childbearing is an important social change that has led to an increasing number of women wishing to slow the rate of reproductive aging
Due to the limitations of human umbilical cord mesenchymal stem cells (HUMSCs) transplantation and the lack of reports from clinically relevant studies, this method has not been widely used in the clinical treatment of female reproductive aging patients, and its clinical efficacy and safety still need further study
In a perimenopausal rat model, HUMSCs transplanted through the tail vein can increase estradiol (E2) and antiMüllerian hormone (AMH) in the ovaries through up to 28 days of paracrine action—by secreting hepatocyte growth factor (HGF), Vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1), improving ovarian architecture and increasing follicles (Li et al, 2017); In clinical trials, in vitro, umbilical cord mesenchymal stem cells on collagen scaffolds activated primordial follicles by phosphorylating FOXO3a and FOXO1; in vivo
Summary
Delaying childbearing is an important social change that has led to an increasing number of women wishing to slow the rate of reproductive aging. Natural aging (Yang et al, 2020) and knockout (Persani et al, 2010; Chen et al, 2020) models can be used, the latter being useful to study known or suggested genetic causes of POI In these models, the therapeutic effects of HUMSCs are assessed by a range of aspects of ovarian function, including follicular development, granulosa cell apoptosis, neoangiogenesis, serum hormone levels and, most importantly, pregnancy rates. The results observed normal clinical behavior in all patients without serious side effects and treatment-related complications; after stem cell treatment, POI patients with shorter amenorrhea appeared to be more likely to obtain mature follicles, while patients with better ovarian status were more likely to have better outcomes with HUMSCs injection, and 4 POI patients had successful clinical deliveries after HUMSCs transplantation This suggests that clinical transplantation of HUMSCs rescued ovarian function in patients with POI, as evidenced by increased follicular development and improved egg collection. Due to the limitations of HUMSCs transplantation and the lack of reports from clinically relevant studies, this method has not been widely used in the clinical treatment of female reproductive aging patients, and its clinical efficacy and safety still need further study
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