Table 1.
Markers and therapeutic effects of reported MSC-derived EVs which contribute to ameliorating female reproductive disorders.
| EVs Resource | Species Resources | EVs markers | Major findings | Reference |
|---|---|---|---|---|
| ADSCs-Exo | Rat/ Human |
Alix/ CD9/ CD63/ CD81 |
1. IUA rat model: Improved endometrial thickness and glands; Decreased fibrotic area; Increased pregnant rate and the number of implanted embryos; Decreased conception time. 2. POI mice model: Increased the number of primordial primary secondary and antral follicles; Increased the level of E2 and AMH; Decreased FSH level; Improved proliferation rate and Inhibited apoptosis of GCs; Increased number of FSHR+/AMH+ GCs and FOXL2+CYP19A1+ GCs. 3. In vitro model: Promoted cell growth and inhibited apoptosis of CCs from PCOS patients. |
(21, 30, 31) |
| UCMSCs-Exo | Human | Alix/ CD9/ CD63/ CD81/ Hsp70/ TSG101 |
1. IUA rat model: Promoted epithelium repair and neovascularization; Improved endometrial thickness and glands; Decreased fibrotic area; Decreased IL-1, IL-6, TNF-α; Increased CD140b, RUNX2, and ER/PR; Increased pregnant rate and implantation sites. 2. TE rat model: Improved proliferation of endometrium; Upregulated VEGF and Bcl-2 level; Decreased caspase-3 level. 3. POI rat/mice model: Decreased the apoptosis and stress of damaged GC; Increased E2 and AMH level; Decreased FSH level; Improved ovarian weight, follicle number, and oocyte retrieved; Reduced conception time; Improved offspring weight; Anti-apoptosis of GCs; Attenuated ROS level. 4. In vitro model: Anti-apoptosis; Increased Ki-67 level and follicular count; Increased E2 and AMH; Decreased FSH and ROS level of GCs from POI women. |
(29, 32–37) |
| UCMSCs-MVs | human | CD9 CD63/ TSG101 |
1. POI mice model: Increased body weight, follicular number and E2 level; Decreased atretic follicles and FSH level; Promoted angiogenesis. | (38) |
| BMSCs-Exo | Rabbit/ Rat/ Mice |
CD9/ CD63/ CD81/ HSP70 |
1. IUA rabbit model: Increased endometrial glands number; Decreased fibrotic area; Reversed EMT. 2. IUA rat model: Improved endometrial thickness and glands; Decreased fibrotic area. 3. POI rat/mice model: Restore normal estrous cycle; Increased follicular number, E2, and AMH; Decreased FSH and LH; Improved GCs viability. |
(39–42) |
| AMSCs-MVs | equine | / | 1. In vitro model: Improved endometrial cell proliferation and anti-apoptosis of LPS-treated cells; Decreased TNF-α, IL-6, MMP1, and MMP13 level. | (43) |
| AMSCs-Exo | human | Alix/ CD9/ CD63/ CD81/ TSG101 |
1. POI mice model: Anti-apoptosis and elevated proliferation in ovaries; Repressed oxidative stress genes in ovaries; Restore follicular numbers; Increased E2 and AMH level; Decreased FSH level; Promote oogenesis. 2. In vitro POI model: Anti-apoptosis of GCs induced by CTX. |
(44) |
| AFMSCs-Exo | Rat/ mice |
/ | 1. POI rat/mice model: Increased AMH; Decreased PTEN and caspase3; Increased estrous cycle; Improved viable offspring and follicular count; Prevented follicular atresia; Anti-apoptosis of damaged GCs | (45, 46) |
| uMSCs-Exo | rat | / | 1. IUA rat model: Decreased fibrotic area; Increased MMP-2 and MMP-9 level; Decreased TIMP-1 level; Increased CD31 and VEGF level. | (47) |
| endMSCs-EVs | Human menstrual blood | CD9/ CD63 |
1. Embryo maturation: Improved total cell the number of embryos obtained from murine and blastocyst hatching rate. 2. IVF murine model: Improved embryos yield and quality in aged Murine. |
(48, 49) |
EVs, Extracellular Vesicles; EXO, Exosomes; MVs, Microvesicles; MSCs, Mesenchymal stem cells; ADSCs, Adipose-derived MSCs; UCMSCs, Umbilical cord-derived MSCs; BMSCs, Bone marrow MSCs; AMSCs, Amniotic MSCs; AFMSCs, Amniotic fluid MSCs; uMSCs, uterus derived MSCs; endMSCs, endometrial MSCs; IUA, Intrauterine adhesion; POI, premature ovarian insufficiency; TE, Thin endometrium; E2, Estradiol; GCs, Granulosa cells; CCs, Cumulus cells; FSH, Follicle-Stimulating Hormone; LH, Luteinizing hormone; AMH, Anti-Mullerian hormone; CTX, Cyclophosphamide; ROS, Reactive oxygen species; IVF, In vitro fertilization; LPS, Lipopolysaccharides; MVD, Micro-vascular density; HUVECs, Human umbilical vein endothelial cells; IL, Interleukin; TNF-α, Tumor necrosis factor alpha; MMP, Matrix metalloproteinase; TIMP, Tissue inhibitor of metalloproteinase; VEGF, Vascular endothelial growth factor; ER, Estrogen receptor; PR, Progesterone receptor; ECM, Extracellular matrix.