Mesenchymal Stem Cells-Derived Exosomes as Dexamethasone Delivery Vehicles for Autoimmune Hepatitis Therapy

Abstract

Exosomes (Exos) are nanosized vesicles (around 100 nm) that recently serve as a promising drug carrier with high biocompatibility and low immunogenicity. Previous studies showed that Exos secreted from mesenchymal stem cells (MSCs) provide protection for concanavalin A (Con A)-induced liver injury. In this study, the protective effect of Exos is confirmed, and dexamethasone (DEX)-incorporated Exos named Exo@DEX are prepared. It is then investigated whether Exo@DEX can function more efficiently compared to free drugs and naive Exos in a Con A-induced autoimmune hepatitis (AIH) mouse model. The results show that Exo@DEX efficiently improves the accumulation of DEX in AIH in the liver. These data suggest that Exo@DEX is a promising drug carrier for AIH and could have applications in other diseases.

Pooled Analysis of Mesenchymal Stromal Cell-Derived Extracellular Vesicle Therapy for Liver Disease in Preclinical Models

“…In total, 39 studies [ 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ] were included, containing control and EV groups, among which 11 [ 15 , 23 , 26 , 27 , 29 , 32 , 42 , 45 , 46 , 50 , 54 ] added MSC group. The control group received phosphate-buffered saline, saline, or a vehicle.…”

“…The sources of MSCs were humans (n = 25) [ 14 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 29 , 30 , 32 , 34 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 46 , 50 , 52 , 53 , 54 ], mice (n = 10) [ 15 , 31 , 36 , 37 , 38 , 42 , 47 , 48 , 49 , 51 ], and rats (n = 5) [ 27 , 28 , 33 , 35 , 45 ]. MSCs originated from multiple tissues, including bone marrow stromal cells (BMSCs) (n = 16) [ 15 , 19 , 26 , 27 , 28 , 31 , 33 , 35 , 37 , 42 , 45 , 47 , 48 , 49 , 50 , ...…”

“…Three studies established NAFLD models based on a high-fat diet [ 44 , 45 , 46 ]. Four studies established AIH models [ 15 , 47 , 48 , 49 ]; two used hepatic injection of S100 [ 47 , 48 ], and two used Con-A [ 15 , 49 ]. Six studies established hepatic ischemia reperfusion injury (I/RI) models [ 35 , 50 , 51 , 52 , 53 , 54 ] by clamping the hepatic artery and portal vein.…”

Mesenchymal Stem Cell-Derived Extracellular Vesicles in Liver Immunity and Therapy

“…Additionally, in AIH, MSC-EVs carrying dexamethasone (DEX) could target macrophages in the liver, therefore increasing the distribution of DEX in liver tissues and leading to DEX reduction in circulation. As a result, the anti-inflammatory therapeutic effect of DEX was enhanced while its side effects were reduced in mice with ConA-induced AIH (171).…”

Therapeutic potential of exosome‐based personalized delivery platform in chronic inflammatory diseases

“…Due to the excellent drug delivery ability of exosomes in vivo , recent research has explored the therapeutic potential of exosomes against other chronic inflammatory diseases, such as periodontitis, pneumonia and chronic hepatitis [114] , [115] , [116] . Transfection of miR-181b into exosomes via lipofectamine reagent enhanced M2 macrophage polarization and inhibited the inflammatory response by activating the PRKCD/AKT signaling pathway, which subsequently promoted osteointegration in vivo [117] .…”