Diagnostic and Therapeutic Roles of Extracellular Vesicles in Aging-Related Diseases

Table 2

Therapeutic effects of EVs from different sources in aging-related diseases.

Disease	Source of EVs	Animal model	Mechanism(s) and effect(s)	Refs.
AD	NSCs	APP/PS1 mice	Increased the metabolism and function of mitochondria, the activation of SIRT1, and the activity and integrity of synapses; decreased the oxidative damage of cerebral cortex and the inflammatory response	[46]
	hNSCs	5xFAD mice	Mitigated AD-related behavioral and molecular neuropathologies	[47]
	MSCs	J20 AD transgenic (Tg) mice	Improved brain metabolism and cognitive function; reduced Aβ plaque load and inhibited astrocyte activation	[48]
	MSCs	3xTg AD mice	Dampened microglia activation and reduced dendritic spine loss	[49]
	ADMSCs	APP/PS1 mice	Decreased the release of inflammatory factors by inhibiting pyroptosis	[50]
	HAs	APP/PS1 mice	HA-Exo provided neuroprotective effects to reverse oligomeric amyloid-β-induced cytotoxicity in vitro	[51]
	Mouse plasma	OA-induced AD mice	Reduced the formation of insoluble NFTs and inhibited CDK5-mediated phosphorylation of tau	[52]
Osteoporosis	BMSCs	OVX-induced postmenopausal osteoporosis mice	miR-29b-3p in EVs potentiated osteogenic differentiation through SOCS1/NF-κB pathway	[63]
	Serum of young rats	OVX-induced postmenopausal osteoporosis mice	miR-19b-3p in EVs promoted the osteogenic differentiation of BMSCs	[78]
	hucMSCs	OVX-induced postmenopausal osteoporosis mice and TS-induced hindlimb disuse osteoporosis mice	CLEC11A in EVs promoted the shift from adipogenic to osteogenic differentiation of BMSCs and inhibited bone resorption	[81]
	BMSCs	OVX-induced postmenopausal osteoporosis mice	MALAT1 in EVs promoted osteoblast activity through microRNA-34c/SATB2 axis	[82]
	SHED	OVX-induced postmenopausal osteoporosis mice	miR-346 in EVs rescued impaired BMSC function and recovered bone loss	[83]
	Mid-to-late stage of osteoblasts	OVX-induced postmenopausal osteoporosis mice	Enhanced osteogenesis	[84]
	BMSCs	OVX-induced postmenopausal osteoporosis mice	miR-150-3p in EVs promoted osteoblast proliferation and differentiation	[85]
	BMSCs	OVX-induced postmenopausal osteoporosis mice	miR-29a in EVs promoted angiogenesis and osteogenesis by acting on human venous endothelial cells	[86]
	BMSCs	OVX-induced postmenopausal osteoporosis mice	miR-22-3p in EVs promoted osteogenic differentiation through MYC/PI3K/AKT pathway	[87]
	ECs	OVX-induced postmenopausal osteoporosis mice	miR-155 in EVs inhibited osteoclasts activity by acting on BMMs	[88]
	Bovine milk	OVX-induced postmenopausal osteoporosis mice	Reduced osteoclast presence through RANKL/OPG system	[90]
	Bovine colostrum	GIOP mice	Facilitated preosteoblast proliferation and inhibited osteoclast differentiation	[91]
	hAFSCs	GIOP mice	Ameliorated the differentiation ability of HOB through a redox-dependent regulation of SIRT1	[92]
	hUCB	OVX-induced postmenopausal osteoporosis mice	miR-3960 in EVs promoted osteogenesis and inhibited osteoclastogenesis	[93]
Hypertension	Plasma from WKY	SHR and WKY	Modulated systemic blood pressure as well as structure and function of cardiovascular tissues in both normotensive and hypertensive rats	[94]
	CDCs	Ang II-induced male C57BL/6J mice	EV-YF1 attenuated cardiac hypertrophy and renal injury induced by Ang II infusion, without affecting blood pressure	[95]
	iPS-MSCs	Young and old male C57BL/6 mice	Attenuated aging-associated vascular endothelial dysfunction, arterial stiffness, and hypertension through SIRT1-AMPKα-eNOS pathway	[96]
	Vascular adventitial fibroblasts of normal rats	SHR and WKY	miR-155-5p in EVs inhibited cell migration and proliferation in VSMCs of SHR through suppressing ACE expression, oxidative stress, and inflammation	[97, 98]
HF	hBMSCs	TAC-operated C57B6/J male mice	Regulated the fibrogenic and adhesion pathways, and cellular metabolic process in the damaged heart	[99]
	Normal human cardiomyocytes	Diseased heart tissues received from patients who underwent heart transplantation at UNC Hospital after heart failure	Promoted cardiomyocyte proliferation, decreased programmed cell death, and stimulated angiogenesis in vitro through phosphatase and tensin homolog/Akt pathway	[100]
	iPSC-Pg and iPSC-CMs	Nude mice with permanent left anterior coronary artery occlusion	miRNAs in EVs are effective in the treatment of CHF	[101]
T2DM	hucMSCs	Low concentrations of TNF-α and high glucose medium were used to simulate insulin resistance in human adipocytes	The insulin-stimulated glucose uptake↑; The level of leptin↓; The mRNA expression of sirtuin-1 and insulin receptor substrate-1↑	[102]
	Pancreatic β cells	β cell-specific miR-29a/b/c transgenic mouse (βTG) model	Prediabetic β cells release exosomal miR-29 to reset macrophage inflammatory tone	[103]

Abbreviations: hNSCs: human neural stem cells; ADMSCs: adipose-derived mesenchymal stem cells; OA: okadaic acid; CDK-5: cyclin-dependent kinase 5; OVX-induced: ovariectomized-induced; GIOP: glucocorticoid-induced osteoporosis; SHED: stem cells from human exfoliated decimal teeth; BMMs: bone marrow-derived macrophages; TS-induced: tail suspension-induced; SHR: spontaneous hypertensive rat; WKY: Wistar-Kyoto rat; iPS-MSCs: induced pluripotent stem cell-derived mesenchymal stem cells; SIRT1-AMPKα-eNOS: sirtuin type 1-AMP-activated protein kinase alpha-endothelial nitric oxide synthase; ACE: angiotensin-converting enzyme; CDCs: cardiosphere-derived cells; Ang II: angiotensin II; TAC: transverse aortic constriction; iPSC-Pg: human induced pluripotent stem cell-derived cardiovascular progenitor; iPSC-CM: human induced pluripotent stem cell-derived cardiomyocyte; CHF: chronic heart failure.