Abstract
Liver cirrhosis leads to hepatic dysfunction and life-threatening conditions. Although the clinical efficacy of autologous bone marrow-derived mesenchymal stem cells (BM-MSC) transplantation in alcoholic cirrhosis (AC) was demonstrated, the relevant mechanism has not been elucidated. We aimed to identify the predictive factors and gene/pathways for responders after autologous BM-MSC transplantation. Fifty-five patients with biopsy-proven AC underwent autologous BM-MSC transplantation. The characteristics of responders who showed improvement in fibrosis score (≥1) after transplantation were compared with those of non-responders. BM-MSCs were analyzed with cDNA microarrays to identify gene/pathways that were differentially expressed in responders. Thirty-three patients (66%) were responders. A high initial Laennec score (p = 0.007, odds ratio 3.73) and performance of BM-MSC transplantation (p = 0.033, odds ratio 5.75) were predictive factors for responders. Three genes (olfactory receptor2L8, microRNA4520-2, and chloride intracellular channel protein3) were upregulated in responders, and CD36 and retinol-binding protein 4 are associated with the biologic processes that are dominant in non-responders. Eleven pathways (inositol phosphate, ATP-binding cassette transporters, protein-kinase signaling, extracellular matrix receptor interaction, endocytosis, phagosome, hematopoietic cell lineage, adipocytokine, peroxisome proliferator-activated receptor, fat digestion/absorption, and insulin resistance) were upregulated in non-responders (p < 0.05). BM-MSC transplantation may be warranted treatment for AC patients with high Laennec scores. Cell-based therapy utilizing response-related genes or pathways can be a treatment candidate.
Highlights
Cirrhosis is the end stage of liver injury with chronic necrosis and the inflammation of cells combined with fibrogenic processes, followed by the transformation of normal liver tissue into regenerative nodules [1,2]
The positive influence of MSCs transplantation has been reaffirmed against alcoholic cirrhosis (AC), including clinical trials for autologous bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation to patients with AC, which have shown an affirmative response of MSCs regarding reducing liver cirrhosis and improving liver function [9,10,11]
After 6 months of the BM-MSC transplantation, liver biopsies were performed for the histological analysis of treated AC patients
Summary
Cirrhosis is the end stage of liver injury with chronic necrosis and the inflammation of cells combined with fibrogenic processes, followed by the transformation of normal liver tissue into regenerative nodules [1,2]. The only definitive treatment for advanced liver cirrhosis is liver transplantation [3]. Transplantation has limitations such as deficiency in donors, surgical complications, immunosuppression after transplantation, and high cost [4]. New therapeutic options, such as regeneration, bioartificial liver, and cell-based transplantation are currently under investigation to improve the prognosis of patients with liver cirrhosis [5]. The positive influence of MSCs transplantation has been reaffirmed against alcoholic cirrhosis (AC), including clinical trials for autologous bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation to patients with AC, which have shown an affirmative response of MSCs regarding reducing liver cirrhosis and improving liver function [9,10,11]
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