Abstract
Reproductive disorders, including intrauterine adhesion (IUA), premature ovarian insufficiency (POI), and polycystic ovary syndrome (PCOS), are great threats to female reproduction. Recently, mesenchymal stem cells derived–extracellular vesicles (MSC-EVs) have presented their potentials to cure these diseases, not only for the propensity ability they stemmed from the parent cells, but also for the higher biology stability and lower immunogenicity, compared to MSCs. EVs are lipid bilayer complexes, functional as mediators by transferring multiple molecules to recipient cells, such as proteins, microRNAs, lipids, and cytokines. EVs appeared to have a therapeutic effect on the female reproductive disorder, such as repairing injured endometrium, suppressing fibrosis of endometrium, regulating immunity and anti-inflammatory, and repressing apoptosis of granulosa cells (GCs) in ovaries. Although the underlying mechanisms of MSC-EVs have reached a consensus, several theories have been proposed, including promoting angiogenesis, regulating immunity, and reducing oxidate stress levels. In the current study, we summarized the current knowledge of functions of MSC-EVs on IUA, POI, and PCOS. Given the great potentials of MSC-EVs on reproductive health, the critical issues discussed will guide new insights in this rapidly expanding field.
Highlights
Mesenchymal stem cells (MSCs), a type of adult stem cells, could be harvested from various tissues, including bone marrow, umbilical cord, menstrual blood, endometrial tissue, adipose tissue, etc. [1]
The following keywords were used for the search, alone or in combination: mesenchymal stem cells, extracellular vesicles, exosomes, female reproductive diseases, intrauterine adhesion, thin endometrium, injured endometrium, endometrial fibrosis, premature ovarian insufficiency, premature ovarian failure, diminished ovarian reserve, polycystic ovary syndrome, follicles, in vitro fertilization treatment, angiogenesis, immune regulation, immunosuppressive, collagen remodel, antiapoptosis, oxidative stress, embryo transfer
The resulting articles were selected by screening titles and reviewing full-text of papers, only articles correlating to the interest topics and its relatives were selected for this review
Summary
Mesenchymal stem cells (MSCs), a type of adult stem cells, could be harvested from various tissues, including bone marrow, umbilical cord, menstrual blood, endometrial tissue, adipose tissue, etc. [1]. Given the capacity of self-renewal and differentiation potentials, emerging researches have regarded MSCs as exciting candidates for cell therapy in regenerative medicine [2, 3]. Assisted reproductive techniques (ART) have made a great contribution to improving the pregnancy outcomes of infertile couples, women with intrauterine adhesion (IUA) or premature ovarian insufficiency (POI) are still difficult to conceive even with the help of ART [17, 18]. Considering the abovementioned advantages and great potentials in regenerative medicine, MSCs-EVs hold great promise as an alternative therapy for IUA and POI [19, 20]. We draft this review to summarize the therapeutic effects and mechanisms of MSC-EVs on the abovementioned disorders. The latest studies on the therapeutic effect of MSCEVs on these diseases are provided and the current limitations and future perspectives of MSC-EVs are discussed as well
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