Table 5.

Therapeutic advantages of EVs released by umbilical cord MSCs.

EVs’ Source	Diseases Model	In Vitro and/or In Vivo Experiments	Molecular Mechanism Proposed	Pathophysiological Effects	References
hUCMSC-derived EVs	Liver fibrosis	In vivo	Inactivation of TGF-β1/Smad signaling pathway.	+ Tissue repair + Liver function − Reduction in collagen deposition − Inflammation	[141]
hUCMSC-derived EVs	Acute kidney injury	In vitro and in vivo	Activation of ERK1/2 pathway signaling and inhibition of p38 MAPK pathway signaling.	+ Kidney tubular cell proliferation − Necrosis of the proximal epithelium − Apoptosis	[142]
hWJMSC-derived EVs	Acute kidney injury	In vitro and in vivo	Activation of Nrf2/ARE pathway signaling.	+ Tissue repair − Apoptosis − Oxidative stress	[143]
hUCBMSC-derived EVs	Liver fibrosis	In vivo	Downregulation of the TGF-β-ID1 signaling pathway and regulation of the MMP/TIMP balance.	+ Liver function − Collagen production − HSC proliferation	[144]
hUCMSC-derived EVs	Inflammatory bowel disease	In vitro and in vivo	Regulating the expression of cytokines (decrease in TNF-α, IL-1β, and IL-6 but an increase of IL-10 in colon tissues and the spleen). Inhibition of the expression of IL-7 in macrophages.	− Infiltration of macrophages − Inflammation − Tissue injury	[145]
hUCMSC-derived EVs	Uveoretinitis	In vivo	Activation of MYD88-dependent signaling via Toll-like receptor (TLR) 4 ligands in monocytes, induction of the M2-like macrophage phenotype, and stimulation of CD4+ T cells.	+ Protection of retinal structure + Retinal function − Leukocyte infiltration − Inflammation	[146]
hUCMSC-derived EVs	Myocardial infarction	In vitro	Increase in Bcl-2 in cardiomyocytes and ATP levels. Decrease in oxidative stress and activation of PI3K/Akt pathway signaling.	+ Myocardium regeneration + Cell proliferation in the border zone + Angiogenesis − Cardiac fibrosis − Cardiomyocyte apoptosis	[147]
hUCMSC-derived EVs	Myocardial infarction	In vitro	Inhibition of SOX6 and the JNK3/caspase-3 pathway and activation of AKT.	+ Cardiac repair + Cardiac regeneration + Enhanced myocardial viability − Oxidative stress	[148]
hUCMSC-derived EVs	Endometrial injury	In vitro	Activation of the PTEN/AKT signaling pathway, as well as upregulation of Bcl-2 and downregulation of cleaved caspase-3.	+ Cell survival of damaged cells + Proliferation of damaged cells + Regeneration of tissue − apoptosis	[149]
hUCMSC-derived EVs	Atopic dermatitis	In vitro and in vivo	Suppression of T cell activation via reductions in the levels of IFN-γ (Th1 cell marker), IL-17 (Th17 cell marker), IL-4, IL-5, and IL-13 (Th2 cell marker), and B-cell-mediated serum IgE. Inhibition of NF-κB activity.	− Atopic histopathological symptoms − Allergic responses systemically − Inflammation − Immune responses	[150]
hUCMSC-derived EVs	Wound healing	In vitro	Enrichment in VEGF-A, FGF-2, HGF, and PDGF-BB and TGF-β molecules.	+ Dermal fibroblast proliferation + Keratinocyte proliferation	[151]
hUCMSC-derived EVs	Traumatic spinal cord injury	In vitro and in vivo	Decrease in pro-inflammatory cytokines, such as IL-1β and IL-6.	+ Long-term regenerative processes − Inflammation − Scarring activity	[152]
hWJMSC-derived EVs	Hypoxic–ischemic insult	In vitro	Regulation of caspase 3 (Casp3) transcription.	+ Neuroprotection + Neuroregeneration − Apoptosis − Neurodegeneration	[153]
hUCMSC-derived EVs	Lung cancer	In vitro	Reduction in PTEN protein expression by transferring miR-410.	+ Migration + Growth + Metastasis	[154]
hUCMSC-Ederived EVs	Pancreatic ductal adenocarcinoma	In vitro and in vivo	Downregulation of Smad3 and the mesenchymal marker N-cadherin. Upregulation of Bax.	+ Apoptosis + Cell cycle arrest − Cell proliferation − Invasion	[155]
hUCMSC-Ederived EVs	Breast cancer	In vitro and in vivo	Downregulation of protein levels of E-cadherin and Bax, as well as downregulation of protein levels of N-cadherin, vimentin, Bcl2, and Bcl-xl.	+ Apoptosis − Cell proliferation − Invasion − Migration	[156]
hWJMSC-derived EVs	Bladder carcinoma	In vitro and in vivo	Downregulation of the phosphorylation of Akt protein kinase and activation of p53/p21 and caspase 3.	+ Apoptosis − Cell proliferation − Metastasis	[157]
UCBMSC-derived EVs	Autoimmune encephalomyelitis	In vitro and in vivo	Inhibition of IL-2 signaling.	+ Suppression of T cell proliferation − Inflammation	[158]