Innovations in the treatment of endometrial diseases: Role of human umbilical cord mesenchymal stem cells and their exosomes

Table 1 Animal studies of human umbilical cord-derived mesenchymal stem cells and their derived exosomes in endometrial diseases

Species	Disease	Treatment	Administration	Key findings (↑ increase; ↓ decrease)	Ref.
Rabbit	IUA	hUC-MSCs	Uterine wall injection of 1 × 106 cells	↑ Gland number; ↑ ER & Ki-67 expression; ↓ fibrosis	[22]
Rat	IUA	hUC-MSCs	Intraperitoneal injection of 2 × 106 cells	↓ TGF-β1/Smad3 expression; ↑ CD31 (angiogenesis)	[24]
Mouse	IUA	Cytokine-preconditioned hUC-MSCs	Uterine wall injection of 2 × 104 cells	↓ TNF-α, IL-6, CD301+ macrophages, α-SMA, collagen I; ↑ IL-10; JAK-STAT pathway modulated	[25]
Mouse	IUA	hUC-MSCs	Tail vein injection of 1 × 106 cells	↓ Fibrosis; ↓ collagen deposition	[30]
Mouse	IUA	hUC-MSCs	Tail vein injection of 2 × 105 cells	Improved endometrial architecture; ↑ visible glands	[38]
Mouse	IUA	hUC-MSC-derived exosomes	Tail vein injection (equivalent to 2 × 106 cells)	↓ IL-1β & IL-6; ↑ M2 macrophage polarization; JAK-STAT pathway activated	[32]
Monkey	IUA	hUC-MSCs/HA-GEL	Intrauterine injection of 1-2 × 107 cells in 200 μL HA-GEL	↑ Endometrial thickness; ↑ gland number; ↓ fibrotic area	[80]
Rat	IUA	hUC-MSCs/HA-GEL	Intrauterine injection of 1 × 1010 cells with 300 μL HA-GEL	↑ Number of pregnancy sacs; ↓ inflammatory & fibrotic factors	[79]
Rat	IUA	hUC-MSCs/HA-GEL	Intrauterine injection of 3 × 105 cells in 1 mL HA-GEL	Uterine cavity expansion; ↑ endometrial thickness & glandular cavity; ↑ gland number	[92]
Mouse	IUA	hUC-MSCs/scaffold	Intrauterine injection of 1 × 106 cells with silk fibroin-submucosa scaffold	↑ Gland number; ↓ fibrotic area	[106]
Rat	IUA	hUC-MSC-exosomes/scaffold	Intrauterine injection of 3 × 1010 exosomes with collagen scaffold	Enhanced endometrial regeneration; ↑ fertility rate	[81]
Rat	IUA	hUC-MSC-exosomes + estrogen	Intraperitoneal injection of exosomes + oral estrogen	↓ Fibrosis; uterine cavity expansion; ↑ blood vessels & glands; ↓ TGF-β; ↑ VEGF	[82]
Rat	Thin endometrium	hUC-MSCs	Tail vein injection of 1 × 107 cells	Preserved endometrial structure; ↑ embryo implantation rate; ↓ fibrosis & inflammation; ↑ cell proliferation & vascularization	[26]
Rat	Thin endometrium	hUC-MSCs	Intrauterine injection of 1 × 107 cells	↑ Endometrial thickness, area & gland number; ↑ cell proliferation & angiogenesis	[29]
Rat	Thin endometrium	hUC-MSCs/hydrogel	Tail vein injection of 5 × 106 cells with pluronic F-127 hydrogel	↑ Endometrial thickness & gland number; ↑ neovascularization	[97]
Rat	Thin endometrium	hUC-MSCs/matrigel microspheres	Intrauterine injection of cell-laden microspheres	↑ Endometrial thickness; ↑ fertility rate (25% to 75%)	[98]
Rat	IUA	hUC-MSCs	Sublingual vein injection of 5 × 106 cells	↓ Endometrial fibrosis; ↑ gland quantity	[100]
Mouse	Thin endometrium	hUC-MSCs/hydrogel	Intrauterine injection of 1 × 106 cells in GelMA/SerMA hydrogel	↑ Endometrial thickness; ↓ fibrosis; improved endometrial repair	[101]
Mouse	Thin endometrium	hUC-MSCs/hydrogel	Intrauterine injection of 5 × 105 cells in alginate-rCo III hydrogel	Restored endometrial function; induced mesenchymal-epithelial transition; ↑ endometrial regeneration & fertility	[102]
Rat	Endometriosis	hUC-MSCs	Tail vein injection of 1 × 105 cells (3 doses)	↓ Nerve fiber density in lesions; ↓ pain symptoms	[43]

IUA: Intrauterine adhesion; hUC-MSCs: Human umbilical cord-derived mesenchymal stem cells; ER: Estrogen receptor; TGF-β: Transforming growth factor β; CD31: Cluster of differentiation 31; TNF-α: Tumor necrosis factor alpha; IL: Interleukin; α-SMA: Alpha-smooth muscle actin; JAK: Janus kinase; STAT: Signal transducer and activator of transcription; M2: Macrophage type 2; HA-GEL: Hyaluronic acid gel; VEGF: Vascular endothelial growth factor; GelMA: Gelatin methacryloyl; SerMA: Sericin methacryloyl; Alginate-rCo III: Alginate-recombinant collagen III.