The Effectiveness and Safety for Mesenchymal Stem Cell for Alcoholic Liver Cirrhosis

Summary

Background \& Aim: Bone marrow derived mesenchymal stem cells (BM-MSCs) have capacity to differentiate into hepatocytes and anti-fibrotic effect in the experimental model. No study was done in humans with alcoholic liver cirrhosis. The researchers investigated the anti-fibrotic effect of BM-MSCs in alcoholic cirrhosis as Phase II clinical study. Methods: Eleven alcoholic cirrhosis patients (M:F = 10:1) with Child-Pugh's class B and maintenance of alcohol abstinence at least 2 months were enrolled. At baseline, all patients received liver biopsy, hepatic venous pressure gradient (HVPG) measurement and serologic tests. BM-MSCs were isolated from each patient's BM and amplified for one month and injected two times at 4, 8week through Rt. hepatic artery. 5x106cells/mL of BM-MSCs were injected in each session. Follow up biopsy, HVPG and relative expression of tissue transforming growth factor-1 (TGF-β1), α smooth muscle actin (α-SMA) and collagen-1 by real time RT PCR were measured after 12weeks from 2nd BM-MSC injection. The primary outcome was improvement in patients' histology Aim : The researchers aimed to evaluate safety and effectiveness of new therapy with bone marrow derived autologous mesenchymal stem cell for hepatic failure caused by alcoholic liver cirrhosis.

Timeline

Start

2009-09

Primary completion

2013-06

Completion

2013-08

Publications

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• Background Batts KP, Ludwig J. Chronic hepatitis. An update on terminology and reporting. Am J Surg Pathol. 1995 Dec;19(12):1409-17. doi: 10.1097/00000478-199512000-00007.
• Background Hong SH, Gang EJ, Jeong JA, Ahn C, Hwang SH, Yang IH, Park HK, Han H, Kim H. In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochem Biophys Res Commun. 2005 May 20;330(4):1153-61. doi: 10.1016/j.bbrc.2005.03.086.
• Background Lee KD, Kuo TK, Whang-Peng J, Chung YF, Lin CT, Chou SH, Chen JR, Chen YP, Lee OK. In vitro hepatic differentiation of human mesenchymal stem cells. Hepatology. 2004 Dec;40(6):1275-84. doi: 10.1002/hep.20469.
• Background Kang XQ, Zang WJ, Bao LJ, Li DL, Song TS, Xu XL, Yu XJ. Fibroblast growth factor-4 and hepatocyte growth factor induce differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocytes. World J Gastroenterol. 2005 Dec 21;11(47):7461-5. doi: 10.3748/wjg.v11.i47.7461.
• Background Kallis YN, Alison MR, Forbes SJ. Bone marrow stem cells and liver disease. Gut. 2007 May;56(5):716-24. doi: 10.1136/gut.2006.098442. Epub 2006 Dec 4. No abstract available.
• Background Wang JA, Luo RH, Zhang X, Xie XJ, Hu XY, He AN, Chen J, Li JH. Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction. J Zhejiang Univ Sci B. 2006 Aug;7(8):641-7. doi: 10.1631/jzus.2006.B0641.
• Background Kim MY, Cho MY, Baik SK, Park HJ, Jeon HK, Im CK, Won CS, Kim JW, Kim HS, Kwon SO, Eom MS, Cha SH, Kim YJ, Chang SJ, Lee SS. Histological subclassification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical stage and grade of portal hypertension. J Hepatol. 2011 Nov;55(5):1004-9. doi: 10.1016/j.jhep.2011.02.012. Epub 2011 Feb 24.
• Jang YO, Kim YJ, Baik SK, Kim MY, Eom YW, Cho MY, Park HJ, Park SY, Kim BR, Kim JW, Soo Kim H, Kwon SO, Choi EH, Kim YM. Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study. Liver Int. 2014 Jan;34(1):33-41. doi: 10.1111/liv.12218. Epub 2013 Jun 19.

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