Table 2.
Outcomes of studies applying hUC-MSCs or their derivatives (with or without bioengineered scaffolds) to treat ovarian pathologies.
| Treatment | Model | Condition | Administration | Results | Reference | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Ovarian Morphology | Developing Follicles | Serum Hormone Levels | Estrous Cyclicity | Markers of Regeneration and Function | Fertility Outcomes | |||||
| hUC-MSC | Rat | POI | TV | Improved | Improved | ↑ E2, AMH ↓ FSH |
NR | ↑ HGF, VEGF, IGF1 | NR | [180] |
| hUC-MSC | Rat | POI | TV | Improved | Improved | ↑ E2, P4, AMH | Restored | ↑ Cell proliferation ↓ Apoptosis ↑ AMH, Bcl-2, FSHR ↓ Caspase-3 |
NR | [186] |
| hUC-MSC | Rat | POI | TV | Improved | Improved | ↑ E2, AMH, GnRH ↓ FSH |
Restored | ↑ Cell proliferation ↓ Apoptosis ↑ NGF, TrkA ↓ FSHR, Caspase-3 |
NR | [84] |
| hUC-MSC | Rat | POI | TV | Improved | Improved | ↑ E2, LH ↓ FSH |
NR | ↓ Apoptosis | NR | [182] |
| hUC-MSC | Mouse | POI | TV | Improved | Improved | ↑ E2 ↓ FSH |
Restored | NR | Restored | [181] |
| hUC-MSC | Mouse | POI | TV | Improved | Improved | ↑ E2, AMH ↓ FSH |
NR | ↑ Cell proliferation ↑ FSHR, Inhibin α/β |
Restored | [187] |
| hUC-MSC (CD146+/−) | Mouse | POI | TV | Improved | Improved | ↑ E2, LH ↓ FSH |
NR | ↑ Cell proliferation ↑ IL-2, TNFα |
Restored | [185] |
| hUC-MSC | Mouse | POI | TV | Improved | Improved | ↑ E2, P4 ↓ FSH |
NR | ↑ IL-4 ↓ IFNγ, NK |
NR | [194] |
| hUC-MSC | Mouse | POI | TV | Improved | Improved | ↑ E2 ↓ FSH |
Restored | NR | NR | [183] |
| hUC-MSC | Mouse | POI | TV | NR | NR | NR | NR | NR | NR | [184] |
| hUC-MSC | Rat | POI | Local | ↑ | NR | NR | NR | NR | NR | [188] |
| hUC-MSC | Mouse | POI | Local | Improved | Improved | ↑ E2, AMH ↓ FSH |
NR | NR | Restored | [37] |
| hUC-MSC | Mouse | POI | Local | Improved | NR | ↑ E2, LH ↓ FSH |
NR | ↑ VEGF | Restored | [189] |
| hUC-MSC | Human | POI | Local | Improved | Improved | NR | NR | NR | Restored | [193] |
| hUC-MSC | Rat | POI | IP | NR | Improved | ↑ E2, LH ↓ FSH |
NR | ↓ Fibrosis | Restored | [190] |
| hUC-MSC | Rat | POI | TV vs. local | Improved | Improved | ↑ E2, AMH, LH ↓ FSH |
Restored | ↓ Apoptosis | Restored | [191] |
| hUC-MSC | Rat | POI | TV vs. local | NR | Improved | NR | NR | ↓ Apoptosis | NR | [36] |
| hUC-MSC | Rat | POI | TV vs. local | Improved | Improved | ↑ E2 ↓ FSH |
Restored | NR | Restored | [31] |
| hUC-MSC | Mouse | POI | NR | NR | Improved | ↑ E2 | NR | ↓ Apoptosis | NR | [35] |
| hUC-MSC | Mouse | Aging | TV vs. local | Improved | Improved | ↑ E2, P4 | Restored | ↓ Apoptosis ↓ ROS production |
Restored | [192] |
| hUC-MSC + collagen | Mouse | POI | Local | Improved | Improved | ↑ AMH, LH ↓ FSH |
Restored | ↑ Cell proliferation ↑ Angiogenesis |
NR | [201] |
| hUC-MSC + collagen | Human | POI | Local | Improved | Improved | ↑ E2 ↓ FSH |
NR | NR | Restored | [200] |
| hUC-MSC + HA | Mouse | POI | Local | Improved | Improved | NR | NR | ↓ Apoptosis | Restored | [197] |
| hUC-MSC vs. HGF | Mouse | POI | Local | NR | Improved | NR | NR | NR | NR | [198] |
| hUC-MSC + AF | Rat | Abdominal adhesions | IP | Improved | Improved | NR | NR | NR | NR | [196] |
| hUC-MSC EV | Mouse | POI | TV | Improved | Improved | ↑ E2 ↓ FSH |
Restored | ↓ Apoptosis | Restored | [204] |
| hUC-MSC exosomes | Mouse | POI | IP | NR | Improved | ↑ E2, AMH ↓ FSH |
Restored | ↑ Cell proliferation | Restored | [205] |
| hUC-MSC exosomes | Mouse | POI | Local | Improved | Improved | ↑ E2, AMH ↓ FSH |
NR | ↑ Cell proliferation ↓ Apoptosis ↓ ROS production |
Restored | [48] |
| hUC-MSC vesicles | Mouse | Aging | Local | NR | Improved | ↑ E2 ↓ FSH |
Restored | ↑ Oocyte quality | Restored | [49] |
| hUC-MSC microvesicles | Mouse | POI | Vena caudalis injection | Improved | Improved | ↑ E2 ↓ FSH |
Restored | ↑ Angiogenesis ↑ VEGF, IGF1, Ang, AKT, p-AKT |
NR | [107] |
| hUC-MSC culture medium | Mouse | POI | IP | Improved | Improved | ↑ AMH | NR | NR | NR | [82] |
| hUC-MSC + hUC-PRP | Rat | POI | Local | Improved | NR | ↑ E2, AMH ↓ FSH |
Restored | ↑ Angiogenesis ↓ Apoptosis |
NR | [210] |
| G-CSF vs. UC plasma | Mouse | POI | TV | Improved | Improved | NR | NR | ↑ Cell proliferation ↑ Angiogenesis |
Restored | [61] |
| GM-CSF | Rat | POI | IP | NR | Improved | NR | NR | ↑ CYP17, CD45 | NR | [158] |
| EGF + Matrigel | Mouse | POI | Local | NR | Improved | NR | NR | NR | Restored | [209] |
The up and down arrows, respectively, indicate an increase and decrease. hUC-MSC, human umbilical cord mesenchymal stem cells; POI, premature ovarian insufficiency; E2, estrogen; AMH, anti-Müllerian hormone; FSH, follicle-stimulating hormone; NR, Non-reported; HGF, hepatocyte growth factor; VEGF, vascular endothelial growth factor; IGF1, insulin growth factor 1; P4, progesterone; Bcl-2, B-cell lymphoma 2; FSHR, follicle-stimulating hormone receptor; GnRH, gonadotropin-releasing hormone; NGF, nerve growth factor; TrkA, tropomyosin receptor kinase A; LH, luteinizing hormone; hUC-PRP, human umbilical cord platelet-rich plasma; CD146, cluster of differentiation 146; IL-2, interleukin 2; TNFα, tumor necrosis factor alpha; IL-4, interleukin 4; IFNγ, interferon gamma; NK, natural killer cells; ROS, reactive oxygen species; HA, hyaluronic acid; HGF, hepatocyte growth factor; AF, amniotic fluid; EVs, extracellular vesicles; AKT, protein kinase B; p-AKT, phosphorylated-protein kinase B; Ang, angiogenin; G-CSF, granulocyte colony-stimulating factor; CYP17, cytochrome P450 17α-hydroxylase/17,20-lyase; CD45, cluster of differentiation 45; GM-CSF, granulocyte–macrophage colony-stimulating factor; EGF, endothelial growth factor; TV, tail vein injection; IP, intraperitoneal injection.