Table 2.

Effects of engineered extracellular vesicles in kidney disease models

Extracellular vesicle origin	Engineering approach	Model	Type of injury	Effects	Ref.
Urine	Klotho expression	Rhabdomyolysis	AKI	Increased endogenous klotho levels and reduced αSMA and CTGF levels in kidney cells	114
RAW 264.7 macrophages	Loading with IL-10	IRI	AKI	Suppressed mammalian target of rapamycin signalling and promoted mitophagy and M2 macrophage polarization, which can suppress inflammation	137
Bone marrow MSCs	Transfection with specific miRNA mimics (miR-10a, miR-127 and miR-486)	Rhabdomyolysis	AKI	Reduced tubular cell injury at a lower therapeutic dose than naïve extracellular vesicles	138
	Transfection with let-7i-5p antagomir	UUO	CKD	Reduced let-7i-5p level in kidney tubular epithelial cells, ECM deposition and EMT and increased activation of TSC1–mTOR signalling	144
Kidney MSCs	Lentiviral transfection of human EPO mRNA	Renal anaemia	CKD	Induced EPO expression in kidney cells, increased haemoglobin levels and decreased serum creatinine and BUN	143
Adipose MSCs	Lentiviral transfection of GDNF mRNA	UUO	CKD	Activated the SIRT1–eNOS signalling pathway in proximal tubular cells and reduced fibrosis	145
Umbilical cord MSCs	Lentiviral transfection of OCT4 mRNA	IRI	AKI	Reduced apoptosis and increased proliferation of renal tubular epithelial cells	146
Human placental MSCs	Encapsulation of extracellular vesicles within a hydrogel containing Arg-Gly-Asp peptides	IRI	AKI and CKD	Increased efficacy of encapsulated extracellular vesicles compared with free extracellular vesicles	149
	Encapsulation of extracellular vesicles within a collagen matrix	IRI	AKI	Increased efficacy of encapsulated extracellular vesicles compared with free extracellular vesicles	150
Red blood cells	Surface expression of KIM1-binding peptide and cargo expression of P65 and Snai1 siRNAs	IRI and UUO	AKI and CKD	Reduced P-p65 and SNAI1 expression, renal inflammation and fibrosis	152

αSMA, α-smooth muscle actin; AKI, acute kidney injury; CKD, chronic kidney disease; CTGF, connective tissue growth factor; ECM, extracellular matrix; EMT, epithelial-to-mesenchymal transition; eNOS, endothelial nitric oxide synthase; EPO, erythropoietin; IRI, ischaemia–reperfusion injury; KIM1, kidney injury molecule 1; miRNA, microRNA; MSC, mesenchymal stromal cell; mTOR, mammalian target of rapamycin; SIRT1, sirtuin 1; SNAI1, zinc-finger protein SNAI1; TSC1, tuberous sclerosis complex subunit 1; UUO, unilateral ureteral obstruction.