Mesenchymal stem cell-derived extracellular vesicles as next generation drug delivery platforms

Table 3 Therapeutic and mechanistic roles of mesenchymal stem cell-derived extracellular vesicles relevant to drug delivery applications

Disease condition	MSC source	Major EV cargo	Mechanistic pathways modulated	Therapeutic outcome	Experimental model	Ref.
Acute myocardial infarction	Bone marrow MSC-EVs	miR-125b	Suppression of cardiomyocyte apoptosis	↑ Cardiac repair	Mouse	[164]
Myocardial infarction	Bone Marrow MSC-EVs	miR-146a-5p	IL-1 receptor-associated kinase 1/NF-κB signaling	↓ Inflammation, ↑ cardiac function	Rat	[165]
Myocardial ischemia/reperfusion	Bone marrow-MSC-EVs	miR-29c	Phosphatase and tensin homolog/protein kinase B/mammalian target of rapamycin pathway	↓ Autophagy, ↓ infarct size	Mouse	[166]
Acute kidney injury	MSC-EVs	mRNA associated with mesenchymal phenotype	Renal tubular cell survival pathways	↑ Renal recovery	Mouse	[167]
Liver fibrosis	MSC-EVs	Anti-fibrotic mediators	Decreased fibrosis signaling	↓ Reduced liver fibrosis	Mouse	[168]
Osteoarthritis	Bone marrow-MSCs	Regulatory miRNAs	Inhibition of NF-κB signaling, downregulation of cyclooxygenase-2 and inflammatory cytokines	↑ Chondrocyte proliferation and matrix production	In vitro (human cartilage tissues)	[169]
Rheumatoid arthritis	Bone marrow-MSCs-EVs	miR-34a	Cyclin I-activated Ataxia telangiectasia mutated/Ataxia telangiectasia and Rad3-related/p53 pathway	↓ Synovial inflammation	Rat	[170]
Type 1 diabetes mellitus	Adipose-MSCs	Immunomodulatory factors	Increased IL-10 and transforming growth factor-β. Decreased IL-17 and interferon-γ	↑ Glycemic control, ↑ immune balance	Mouse	[171]
Cerebral ischemic/reperfusion injury	Bone marrow-MSCs-EVs	Long non-coding RNA KLF3-AS1	Sirtuin-1 stabilization, miR-206/USP22 axis	↓ Cerebral infarction, ↑ neurological function	Mouse	[172]
Traumatic brain injury	Umbilical cord-MSC-EVs	miRNAs	Suppression of neuronal apoptosis and microglial activation	↑ Neurological function	Rat	[173]
Bacterial pneumonia	Bone marrow-MSC-EVs	Paracrine mediators	Increased alveolar fluid clearance. Reduced bacterial load	Attenuated lung injury	Mouse	[174]
Myocardial ischemia/reperfusion injury	MSC-EVs	Pro-angiogenic factors	Activation of protein kinase B and glycogen synthase kinase-3β pathways	↓ Oxidative stress, ↑ angiogenesis	Mouse	[175]

MSC: Mesenchymal stem cell; EV: Extracellular vesicle; IL: Interleukin; NF-κB: Nuclear factor-kappa B; MSC-EV: Mesenchymal stem cell-derived extracellular vesicle.