Response-Related Factors of Bone Marrow-Derived Mesenchymal Stem Cells Transplantation in Patients with Alcoholic Cirrhosis.
Haripriya GuptaGi Soo YounSang Hak HanMin Jea ShinSang Jun YoonDae Hee HanNa Young LeeDong Joon KimSoon Koo BaikKi-Tae SukPublished in: Journal of clinical medicine (2019)
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.
Keyphrases
- cell therapy
- bone marrow
- binding protein
- mesenchymal stem cells
- extracellular matrix
- insulin resistance
- single cell
- stem cells
- end stage renal disease
- metabolic syndrome
- rheumatoid arthritis
- copy number
- chronic kidney disease
- dna methylation
- small molecule
- patient reported outcomes
- platelet rich plasma
- ultrasound guided
- transcription factor
- umbilical cord
- dna binding
- patient reported