anextClinical application of stem cell-derived exosomes in obstetrics and gynecology
Premature ovarian failure (POF), different from premature menopause (early menopause), usually refers to amenorrhea before the age of 40 in women, accompanied by persistent endocrine abnormalities such as increased follicle-stimulating hormone levels and decreased estrogen levels. In addition, it is also referred to as primary ovarian insufficiency (POI) or premature menopause. There are many premature ovarian failure, involving genetics, autoimmunity, infection, physical and chemical damage and unknown causes, etc., due to the large and complex POF, it is difficult for most patients to only treat the symptoms. At present, the method of POF varies according to whether the patient has fertility requirements, and the main focus of POF patients without fertility requirements is to alleviate symptoms, improve physical and psychological conditions, and prevent or reduce long-term complications. In addition to relieving symptoms, preventing and reducing long-term complications, patients with POF who have fertility requirements also need to take into account fertility.
POI or POF is defined as the loss of ovarian function before the age of 40 years, and non-genetic causes of POI include autoimmune diseases, metabolic conditions, infections, and iatrogenic surgeries (e.g., chemotherapy, radiotherapy, and surgery). Women with POIs experience various complications such as osteoporosis, infertility, cardiovascular disease, and depression. Although timely initiation of hormone replacement** is essential to manage these symptoms and complications, it does not restore ovarian function. Experiments currently being tested include mitochondrial activation, in vitro activation, stem cells, and exosomes.
Umbilical cord MSC-derived exosomes can improve ovarian function in a cyclophosphamide (CTX)-induced POI mouse model. SC-EXO** not only restored hormone levels and follicle counts related to ovarian function, but also improved the reproductive capacity of POI mice. In addition, exosomes promote the proliferation of ovarian granulosa cells (GC) by modulating the HIPo pathway, and this effect is neutralized by YAP inhibitors. Similar results were obtained using exosomes from iPSC-derived MSCs. Studies have shown that umbilical cord MSC-derived exosomes can restore ovarian phenotype and function in a POI mouse model, promote the proliferation of CTX-damaged human GC and oocytes, and alleviate ROS accumulation by delivering exosome miR-17-5P and targeting its downstream messenger ribonucleic acid SIRT7. It was further clarified that miR-17-5P down-regulated the expression of PARP1, H2ax and XRCC6 by inhibiting SIRT7. Bone marrow MSC-derived exosomes can restore the estrous cycle, increase the number of basal and sinus follicles, increase estradiol E2 and anti-Mullerian hormone levels, and decrease follicle-stimulating hormone and luteinizing hormone levels in a chemotherapy-induced POF rat model. Mechanistically, this is achieved by targeting the exosome miR-114-5p of PTEN.