Response-Related Factors of Bone Marrow-Derived Mesenchymal Stem Cells Transplantation in Patients with Alcoholic Cirrhosis

• Main Authors: Haripriya Gupta, Gi Soo Youn, Sang Hak Han, Min Jea Shin, Sang Jun Yoon, Dae Hee Han, Na Young Lee, Dong Joon Kim, Soon Koo Baik, Ki Tae Suk
• Format: Article
• Language: English
• Published: MDPI AG 2019-06-01
• Series: Journal of Clinical Medicine
• Subjects: cirrhosis; bone marrow; mesenchymal stem cells; characteristics; liver regeneration
• Online Access: https://www.mdpi.com/2077-0383/8/6/862

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 (&#8805;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 (<i>p</i> = 0.007, odds ratio 3.73) and performance of BM-MSC transplantation (<i>p</i> = 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 (<i>p</i> &lt; 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.