Comparative Evaluation of Anti-Fibrotic Effect of Tissue Specific Mesenchymal Stem Cells Derived Extracellular Vesicles for the Amelioration of CCl4 Induced Chronic Liver Injury

Abstract

Mesenchymal Stem Cells (MSCs) derived Extracellular Vesicles (EVs) have emerged as an effective candidate for amelioration of liver fibrosis. However, the effect and the mechanisms of MSC-EVs in liver repair remains elusive. In this study, we have evaluated the differential regenerative efficacy of EVs derived from two different human tissue-specific MSCs (Adipose tissue; AD-MSC and Wharton's Jelly; WJ-MSC), in a murine model of chronic liver fibrosis. Mouse model of chronic liver injury was induced by carbon tetrachloride (CCl 4 ) injection, followed by administration of EVs via the tail vein. Both quantitative and qualitative assessment was done to evaluate the hepatic regenerative potential of tissue specific MSC-extracellular vesicles. EVs, regardless of their MSC source, were found to be effective in alleviating chronic liver fibrosis, as demonstrated by macroscopic alterations in the liver. According to the findings of the comprehensive study, there were subtle variations in the tissue specific MSCs-EVs mediated approaches. A greater anti-fibrotic impact was demonstrated by AD-MSC derived EVs through extracellular matrix alteration and hepatocyte proliferation. WJ-MSC EVs, on the other hand, have an anti-inflammatory effect, as evidenced by alterations in the expression of pro-and anti-inflammatory cytokines. Furthermore, cargo profiling of these EVs revealed differences in the miRNA and protein expression, as well as the pathways that they were associated.

An Overview of Current Research on Mesenchymal Stem Cell-Derived Extracellular Vesicles: A Bibliometric Analysis From 2009 to 2021

“…Given the different types and abundance of proteins and RNAs in EVs derived from different MSCs, the selection of tissue-specific MSCs should be based on the pathological characteristics of diseases. According to available studies, ADSCs-derived EVs contained high levels of proangiogenic factors, BMSCs-derived EVs enriched with prodifferentiation and chemotactic proteins, and EVs secreted by hUCMSCs exhibited strong anti-inflammatory effects (Gorgun et al, 2021;Gupta et al, 2022). Therefore, further studies are warranted to elucidate the specific effects of different sources of MSC-EVs on various physiological processes and their strength, to guide application in disease therapy.…”

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 , ...…”

“…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 , 51 ], umbilical cord-derived mesenchymal stem cells (UCMSCs) (N = 8) [ 14 , 38 , 41 , 43 , 44 , 52 , 53 , 54 ], adipose tissue-derived stem cells (ADSCs) (n = 7) [ 20 , 21 , 22 , 32 , 36 , 39 , 46 ], embryonic stem cells (ESCs) (n = 4) [ 23 , 24 , 30 , 40 ], amnion stem cells (AMSCs) (N = 2) [ 18 , 25 ], menstrual blood-derived stem cells (MenSC) (N = 1) [ 34 ], and tonsil-derived stem cells (TSCs) (n = 1) [ 22 ]. Gupta et al [ 20 ] and Haga et al [ 37 ] applied two types of MSC-derived EV to establish liver damage models.…”

“…The drugs mainly involved carbon tetrachloride (CCl 4 ), thioacetamide (TAA), D-galactosamine (D-GalN), lipopolysaccharide (LPS) (D-GalN/LPS), TNF-α/D-GalN, and diethylnitrosamine (DEN). Sixteen studies used chronic liver injury or liver fibrosis models [ 14 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Only one study used an FVB (Abcb4 tm1Bor ) mouse model of PSC, which was classified as a liver fibrosis model.…”