Table 1.

Pre-clinical studies showing the efficacy of exosomes in improving cardiovascular function

Source of exosomes	Type	miRNAs involved	Model	Effect	References
“Healthy” biological fluids	Pericardial fluids	let-7b-5p	In vitro	Improve cell viability Increase proliferation Increase networking capabilities	[49]
	Normotensive Wistar Kyoto rat plasms	–	In vivo	Decreased systolic blood pressure Reduced fibrosis Reversed hypertensive structural changes	[166]
	Heart tissue of exercised db/db mice	miRNA-29b miRNA-455	In vivo	Reduced cardiac MMP9 expression and function	[109]
Primary cardiomyocytes/CDC/CPC	CDC	miRNA-146a	In vitro	Promote angiogenesis Promote proliferation Decrease cell death	[104]
			In vivo	Promote angiogenesis Promote cardiac regeneration
	Hypoxic CPC	miRNA-320, miRNA-222, miRNA-185	In vitro	Promote angiogenesis	[105]
			In vivo	Improve cardiac function Reduce fibrosis
Endothelial cells/EPCs/Epithelial cells	EPC	miRNA-21a-5p miRNA-222-3p miRNA-221-3p miRNA-155-5p miRNA-29a-3p	In vivo	Reduced atherosclerotic plaques Ameliorate endothelium-dependent contractile dysfunction Reduce oxidative stress and inflammatory factors Improve vasodilation	[139]
	EPC	–	In vivo	Accelerate cutaneous wound healing	[177]
			In vitro	Promote migration Promote proliferation Promote tube formation Increase pro-angiogenic molecules
	Endothelial cells	miRNA-126	In vivo	Improves neurological and cognitive function Increase axon density Increase myelin density Increase vascular density Increase arterial diameter	[26]
			In vitro	Increased primary cortical neuron axonal outgrowth Increases endothelial capillary tube formation
Stem cells	human umbilical cord MSC	-	In vitro	Reduce cardiomyocyte apoptosis Promote tube formation Promote migration	[97]
			In vivo	Increase LV function Reduced fibrosis
	human umbilical cord MSC	miRNA-19a	In vitro	Increased proliferation and migration Decreased apoptotic rate and proteins	[178]
			In vivo	Improved cardiac function post MI
	hESC-pg	-	In vivo	Improve cardiac function	[107]
	MSC	-	In vivo	Ameliorate myocardial injury Reduce fibrosis and LV collagen	[120]
	MSC	miRNA-21a-5p	In vitro	Reduce pro-apoptotic gene products Reduced cel death in response to oxygen-glucose deprevation	[106]
			In vivo	Reduce pro-apoptotic gene products Reduce infarct size
	bone marrow-derived macrophages	miRNA-146b miRNA-99a miRNA-378a	In vivo	Suppress inflammation Reduce necrotic lesion Reduce hematopoiesis	[138]
	induced pluripotent stem cells-derived MSC	–	In vivo	Enhance micro vessel density Improve blood perfusion in ischemic limb	[146]
			In vitro	Promote migration Promote proliferation Promote tube formation
	bone marrow MSCs	miRNA-210-3p	In vitro	Promote migration Promote proliferation Promote tube formation	[147]
			In vivo	Increase blood perfusion Formation of new blood vessels
	MenSCs	–	In vivo	Enhance neoangiogenisis Enhanced re-epitheliarisation	[102]
	Adipose-derived stem cell (ADSCs)	miRNA-30d-5p	In vivo	Decreased cerebral injury area Suppress autophagy Promote M2 microglia/macrophage polarization	[156]
			In vitro	Suppress autophagy
	MSC	Let-7a miRNA-23a miRNA-125b	In vivo	Increase myelin thickness and axonal diameters of sciatic nerves Alleviate neurovascular dysfunction Improve functional recovery	[161]
Therapeutically modulated exosomes/ exosomes from therapeutically modulated source	Akt-overexpressing MSCs	–	In vitro	Promote angiogenesis Promote endothelial cell proliferation	[179]
			In vivo	Improve cardiac function Improve blood vessel formation
	Transgenic (TG) mouse model with cardiac-specific overexpression of Hsp20	–	In vitro	Reduce apoptosis Improve angiogenesis	[99]
			In vivo	Promote exosome generation Reduce adverse remodeling Reduce apoptosis
	Atorvastatin pre-treated bone marrow MSCs	miRNA-221-3p	In vivo	Facilitate wound healing Promote blood vessel formation	[149]
			In vitro	Promote migration Promote proliferation Promote tube formation
	Antioxidant polyurethane nerve conduit with bone marrow stem cells derived exosomes	–	In vivo	Improve the neve functionality	[163]
	ADSC exosomes transfected with miRNA-93-5p mimic	miRNA-93-5p	In vivo	Reduce myocardial damage after acute MI Suppressed autophagy and inflammation after MI	[180]
			In vitro	Inhibit hypoxia-induced myocardial cell injury