Response-Related Factors of Bone Marrow-Derived Mesenchymal Stem Cells Transplantation in Patients with Alcoholic Cirrhosis
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.Keywords: bone marrow; characteristics; cirrhosis; liver regeneration; mesenchymal stem cells.
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基因水平:PCR Array、RT-PCR、PCR、单细胞测序
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细胞水平:细胞染色、细胞分选、细胞培养、细胞功能
组织水平:空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析:流式数据分析、组化数据分析、多因子数据分析
基因水平:PCR Array、RT-PCR、PCR、单细胞测序
蛋白水平:MSD、Luminex、CBA、Elispot、Antibody Array、ELISA、Sengenics
细胞水平:细胞染色、细胞分选、细胞培养、细胞功能
组织水平:空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析:流式数据分析、组化数据分析、多因子数据分析
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