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Table 3 Effect of preconditioned and engineered EVs in fibrotic diseases therapy

From: Extracellular vesicles: emerging roles, biomarkers and therapeutic strategies in fibrotic diseases

Precondition/Engineering strategy

Origin

Method

Model

Function

Ref.

hypoxic

BMMSCs

culture MSCs under hypoxia condition (0.5% O2)

mouse MI

improve cardiac function and reduce scar size

[157]

cytokine Preconditioning.

BMMSCs

pretreat MSCs with IL1β, IL6 and TNFα

mouse colitis

induce macrophage M2 polarization, decrease dintestinal fibrosis and angiogenesis

[158]

cytokine preconditioning.

hucMSCs

pretreat MSCs with TNFα

rat urethral stricture

inhibit fibroblast inflammation, suppress urethral fibrosis and stricture

[159]

cargo loading

ADSCs

transfect GDNF into ADSCs via a lentiviral transfection system

mouse UUO

reduce tubulointerstitial fibrosis

[164]

cargo loading

ADSCs

transfect miRNA-181-5p to ADSCs

mouse liver fibrosis

inhibit HSC activation, reduce liver fibrosis

[165]

cargo loading

BMMSCs

transfect CFZF-VPR into BMMSCs via plasmid

human bronchial epithelial cells

activate CFTR

[166]

cargo loading

mouse satellite cells

transfect Lamp2b-RVG vector and miR29 into mouse satellite cells

mouse UUO

target kidney, inhibit TGF-β signaling pathway, alleviate renal fibrosis

[167]

membrane modification

ADSCs

modify the surface of ADSC-EVs with vitamin A derivative by phospholipid insertion

mouse liver fibrosis

target active HSCs, reverse the fibrotic cascade

[169]

combination with biomaterials

BMMSCs

extrude IONP-incorporated MSCs serially and obtain IONP-incorporated NVs

rat MI

improve the retention of EVs in the infarcted heart, reduce cardiac apoptosis, inflammation, and fibrosis

[172]

combination with biomaterials

ADSC/ murine stem cells

combinate EVs with a thermoresponsive hydrogel and inject locally at 4 °C

pig esophageal fistula/rat colon fistula

retain EVs in the entire fistula tract, decrease inflammatory response and fibrosis, increase angiogenesis

[174, 175]

cargo loading, membrane modification

fibroblast

fuse the membrane of clodronate loaded liposome with fibroblast derived EVs and load it with Nintedanib

mouse PF

deplete Kupffer cells, target fibroblast and accumulate in fibrotic lung, reduce lung fibrosis

[170]