Stem cell-derived extracellular vesicles: A novel and potential remedy for primary ovarian insufficiency

Abstract

Primary ovarian insufficiency (POI) is an essential cause of young female fertility loss. At present, there are many treatments for primary ovarian insufficiency, but due to the complexity of the pathogenesis of primary ovarian insufficiency, the efficacy still could not be satisfactory. Stem cell transplantation is a feasible intervention protocol for primary ovarian insufficiency. However, its wide application in the clinic is limited by some defects such as tumorigenic and controversial ethical issues. Stem cell-derived extracellular vesicles (EVs) represent an important mode of intercellular communication attracting increasing interest. It is well documented that stem cell-derived extracellular vesicles for primary ovarian insufficiency with exciting therapeutic effects. Studies have found that stem cell-derived extracellular vesicles could improve ovarian reserve, increase the growth of follicles, reduce follicle atresia, and restore hormone levels of FSH and E2. Its mechanisms include inhibiting ovarian granulosa cells (GCs) apoptosis, reactive oxygen species, and inflammatory response and promoting granulosa cells proliferation and angiogenesis. Thus, stem cell-derived extracellular vesicles are a promising and potential method for primary ovarian insufficiency patients. However, stem cell-derived extracellular vesicles are still a long way from clinical translation. This review will provide an overview of the role and the mechanisms of stem cell-derived extracellular vesicles in primary ovarian insufficiency, and further elaborate on the current challenges. It may suggest new directions for future research.

Stem cells and exosomes: as biological agents in the diagnosis and treatment of polycystic ovary syndrome (PCOS)

“…The ability to transform into a differentiated cell decreases from the first category to the third category, respectively (25, 26, 28). Based on the above content and recent studies, it can be theorized that stem cells have a high capacity for the treatment of various diseases (Figure 3) (26,33,39).…”

“…Each type has distinct characteristics and differentiation potentials, making them valuable for various research and medical applications (28-31). ESCs are created from the derivatives of the epiblast layer in the inner layer of the blastocyst, which can transform into the three primary germ layers of ectoderm, endoderm, and mesoderm (25, 29,[32][33][34].…”

The remodeling of ovarian function: targeted delivery strategies for mesenchymal stem cells and their derived extracellular vesicles

“…MSCs and MSCs-derived EVs have gradually become the most promising option for POI treatment [ 19 ]. However, in addition to the inherent safety limitations of MSCs themselves, the shortcomings of many of the current POI-related studies are the failure to address the non-targeted distribution of MSCs and MSCs-derived EVs in various organs with minimal distribution in the ovary after intravenous injection, especially the blockage in the lungs of MSCs, and the failure to capitalize on the properties of EVs as a nanomedicine carrier [ 20 – 22 ].…”

Research progress of extracellular vesicles in the treatment of ovarian diseases (Review)

“…Moreover, exosomes derived from mesenchymal stem cell (MSC) species regulate androgen production in vitro by virtue of their cargo carrier function as the main molecule for reversing PCOS, thereby restoring fertility in PCOS mice ( 37 ). In the development of POI, EVs derived from a variety of stem cells such as embryonic stem cells and human umbilical cord MSCs (HUCMSCs) play an important role in intercellular communication by transporting several molecules such as miRNAs from donors to recipients through their own transport function leading to the occurrence of increased follicular growth, decreased follicular atresia and restoration of hormone levels, thus playing an important role ( 38 , 39 ). EVs are closely associated with the development of ovarian cancer, POI and PCOS.…”