Table 1.

Main growth factors secreted by hUC-MSCs and found in the acellular components of hUC blood. For each growth factor, this table lists the most prominent signaling pathways, biological functions, and therapeutic applications reported in the literature in reproductive medicine and other medical fields.

Type of Factor	Signaling Pathways	Biological Functions	Therapeutic Applications	References
VEGF	PI3K/AKT Ras/MAPKs Src/FAK	✓Angiogenesis; ✓Vessel permeability; ✓Cell proliferation; ✓Cell motility; ✓Immune cell chemotaxis.	Reproductive medicine: EA, IUA, POI Other fields: Neurodegenerative diseases, chronic diabetic wounds, neuropathic pain	[54,110,139,140]
NGF	PI3K/AKT Ras/MAPKs PLC-ϒ JNK	✓Growth and survival of sensory nerves; ✓Inhibition of apoptosis; ✓Cell proliferation.	Reproductive medicine: POI Other fields: Brain and nerve injury, myocardial infarction, diabetic cystopathy	[84,141,142,143,144]
EGF	PI3K/AKT Ras/MAPKs JAK/STATs	✓Mitosis, differentiation, and chemotaxis in epithelial and mesenchymal cells; ✓Secretion of cytokines.	Reproductive medicine: IUA, POI Other fields: Dry eye syndrome, atopic dermatitis	[124,145]
FGF	PI3K/AKT Ras/MAPKs	✓Proliferation, growth, and differentiation of mesenchymal cells, chondrocytes, and osteoblasts; ✓Angiogenesis.	Reproductive medicine: EA, IUA, vaginal reconstruction Other fields: Autoimmune encephalitis, chronic diabetic wounds, amyotrophic sclerosis, osteoarthritis	[144,146,147,148]
HGF	PI3K/AKT Ras/MAPKs JAK/STATs	✓Regulation of cell migration; ✓Cell growth; ✓Fibrosis inhibition; ✓Regulation of wound healing; ✓Immune modulation.	Reproductive medicine: POI Other fields: Parkinson’s disease, cardiopathies, liver fibrosis	[149,150,151,152]
G-CSF	PI3K/AKT Ras/MAPKs JAK/STATs	✓Cell survival and proliferation; ✓Enhancement of mature neutrophil function.	Reproductive medicine: POI, recurrent implantation failure Other fields: Neurodegenerative diseases, acute liver failure, brain injury	[54,83,153,154,155]
GM-CSF	PI3K/AKT Ras/MAPKs JAK/STATs	✓Activation of macrophages; ✓Differentiation of immune cells; ✓Cell survival and proliferation.	Reproductive medicine: POI Other fields: Lung injury	[156,157,158]
PDGF (*)	PI3K/AKT JAK/STATs Ras/MAPKs PLC-ϒ	✓Mitosis and chemotaxis of mesenchymal-origin cells; ✓Activation of macrophages; ✓Angiogenesis and blood vessel repair.	Reproductive medicine: IUA Other fields: Chronic diabetic wounds, acute kidney injury, liver fibrosis, lung diseases	[159,160,161,162,163]
TGFβ	Canonical: SMAD Non-canonical: PI3K/AKT Ras/MAPKs	✓Collagen synthesis; ✓Angiogenesis; ✓Cell chemotaxis; ✓Cell growth; ✓Inhibition of osteoclast formation and bone resorption; ✓Promotion of wound healing; ✓Inhibition of apoptosis; ✓Remodeling of the ECM.	Reproductive medicine: IUA, POI, breast cancer Other fields: Atopic dermatitis, liver fibrosis, renal fibrosis, lung injury, wounds	[87,164,165,166,167,168]
ILs	PI3K/AKT Ras/MAPKs JAK/STATs	✓Chemotaxis; ✓Cell proliferation; ✓Angiogenesis; ✓Immune modulation.	Reproductive medicine: IUA, POI, ovarian carcinoma Other fields: Autoimmune encephalitis, neuropathic pain, spondyloarthritis, brain injury, dermatitis	[139,144,169,170,171,172,173]
CKs	PI3K/AKT Ras/MAPKs JAK/STATs PLC-ϒ	✓Chemotaxis and cell adhesion; ✓Cell growth; ✓Cell proliferation; ✓Release of granules and oxidants.	Reproductive medicine: IUA, POI Other fields: Liver failure, lung injury, brain injury	[94,174,175,176,177,178]

(*) PDGF is secreted by platelets, but it was included in the table because of its key role in acellular therapies. VEGF, vascular endothelial growth factor; NGF, nerve growth factor; EGF, endothelial growth factor; FGF, fibroblast growth factor; HGF, hepatocyte growth factor; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte–macrophage colony-stimulating factor; PDGF, platelet-derived growth factor; TGFβ, transforming growth factor beta; ILs, interleukins; CKs, chemokines; PI3K, phosphoinositide 3-kinase; MAPKs, mitogen-activated protein kinases; PLC-ϒ, phospholipase C-gamma; JNK, c-Jun N-terminal kinase; ECM, extracellular matrix; IUA, intrauterine adhesions; POI, premature ovarian insufficiency.