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Potential benefits of extracellular vesicles as therapeutic agents in IUA
| Donor cell | Animal | Time period | Dose of Evs | Outcomes | Mechanism | Reference |
|---|---|---|---|---|---|---|
| Umbilical cord mesenchymal stem cells | Albino rats | 8 weeks | 100 μg |
Restored endometrial glands in the uterine sections Decreased collagen fiber deposition in the endometrium |
Downregulated TNF-α, TGF-β, IL-1, IL-6, RUNX2, and collagen-I | (80) |
| Umbilical cord-derived mesenchymal stem cells | SD rats | 8 weeks | 100 μl |
Excellent neovascularization Reduced fibrosis formation and promoted collagen remodeling Unregulated ERα positive cells and PR positive areas |
16 miRNA, especially miR-223-3p induced the polarization of macrophages to the M2 phenotype | (79) |
| Rat uterus derived mesenchymal stem cells | Wistar albino rats | 8 weeks | 25 μg |
Supported the formation of blood vessels |
Upreguleated CD31 and VEGFR-1 decreased the MMP-2, MMP-9 and TIMP-2 expressions | (81) |
| Bone marrow mesenchymal stem cells | SD rats | 14 days | None |
Repress endometrial fibrosis and promote functional recovery |
miR-340 in the exosomes reduced the upregulated expression of Collagen I1α, α-SMA and TGF-βR1 | (74) |
| Bone marrow mesenchymal stem cells | Mice | None | 4.1E+9 particles/ml |
Promote cell proliferation and cell migration Repair damaged endometrium |
Overexpress miR-29a to reduce α-SMA, Collagen I, SMAD2, and SMAD3 | (76) |
| Adipose-derived mesenchymal stem cells | SD rats | 8 weeks | 100 μg |
Endometrial regeneration Improves endometrial receptivity and fertility |
Upregulate the expression of VEGF integrin and LIF | (77) |
| Adipose-derived mesenchymal stem cells | SD rats | None | 5 μg |
Inhabit endometrial fibrosis |
lncRNA-MIAT in Exosomes regulate miR-150-5p | (78) |
| Menstrual blood-derived stromal cells | SD rats | 18 days | 4.25×108 particle/ml |
Recovered the morphology and promoted the proliferation of endometrial cells Restore endometrial receptivity and improve the fertility Restored the thickness of endometrium, gland numbers and vascular |
Inhibit TGFβ1/SMAD3 mediated endometrial fibrosis by upregulating BMP7 expression and SMAD1/5/8 and ERK1/2 phosphorylation | (73) |
| Adipose-derived mesenchymal stem cells | SD rats | None | None |
Facilitate the regeneration of the endometrium Enhanced endometrial receptivity Promoted neovascularization Anti-infective Anti-fibrotic activity |
Upregulated HOXA-1, LIF, Integrin β3, IGF-1, VEGF and bFGF | (85) |
SD: Sprague Dawley, TNF: tumor necrosis factor, TGF: transforming growth factor, IL: interleukin, RUNX: runt-related transcription factor, VEGFR: vascular endothelial growth factor receptor, ER: estrogen receptor, PR: progesterone receptor, MMP: matrix metalloproteinase, TIMP: tissue inhibitor of metalloproteinase-1, SMA: smooth muscle actin, VEGF: vascular endothelial growth factor, LIF: leukemia inhibitory factor, IGF: insulin-like growth factor, FGF: fibroblast growth factor.