Preprint Article Version 1 This version is not peer-reviewed

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

Version 1 : Received: 4 June 2019 / Approved: 5 June 2019 / Online: 5 June 2019 (15:43:03 CEST)

A peer-reviewed article of this Preprint also exists.

Gupta, H.; Youn, G.S.; Han, S.H.; Shin, M.J.; Yoon, S.J.; Han, D.H.; Lee, N.Y.; Kim, D.J.; Baik, S.K.; Suk, K.T. Response-Related Factors of Bone Marrow-Derived Mesenchymal Stem Cells Transplantation in Patients with Alcoholic Cirrhosis. J. Clin. Med. 2019, 8, 862. Gupta, H.; Youn, G.S.; Han, S.H.; Shin, M.J.; Yoon, S.J.; Han, D.H.; Lee, N.Y.; Kim, D.J.; Baik, S.K.; Suk, K.T. Response-Related Factors of Bone Marrow-Derived Mesenchymal Stem Cells Transplantation in Patients with Alcoholic Cirrhosis. J. Clin. Med. 2019, 8, 862.

Journal reference: J. Clin. Med. 2019, 8, 862
DOI: 10.3390/jcm8060862

Abstract

Liver cirrhosis leads to hepatic dysfunction and life-threatening conditions. Though clinical efficacy of autologous bone marrow-drived mesenchymal stem cells (BM-MSC) transplantation in alcoholic cirrhosis (AC) was demonstrated, the relevant mechanism has not been elucidated. We aimed to identify 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 genes and pathways that were differentially expressed in responder after transplantation. Thirty-three patients (66%) were responders. In the multivariate analysis, initial high 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 responder. Three genes (olfactory receptor 2L8, microRNA4520-2, and chloride intracellular channel protein 3) were upregulated in responders and 11 metabolic 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 is warranted treatment for AC patients with high Laennec score. Cell-based therapy utilizing response-relating genes or pathway can be treatment candidate.

Subject Areas

Cirrhosis; Bone marrow; Mesenchymal stem cells; Characteristics; Liver regeneration

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