Mesenchymal Stem Cells Treat Liver Cirrhosis

Umbilical Cord Mesenchymal Stem Cell Transfusion in Patients With Severe Liver Cirrhosis

The purpose of this study is to investigate the efficacy of umbilical cord mesenchymal stem cells (MSCs) transfusion in the treatment of liver cirrhosis. Liver function will be monitored by serum analysis. The levels of serum alanine aminotransferase (ALT), total bilirubin (TB), prothrombin time (PT), prealbumin(PA) and albumin (ALB) will be examined at pre-transfusion, and 3 days to 2 years post-transfusion. Child-Pugh scores, Model for End-Stage Liver Disease scores and clinical symptoms will be assessed simultaneously.

Study Overview

• Status: Suspended
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Drug: Conserved Therapy; Procedure: Hepatic artery infusion or Intravenous infusion

Detailed Description

Patients with liver cirrhosis will be randomly divided into three groups. Umbilical cord MSCs will be infused to patients using interventional method via hepatic artery for one group. The catheter will be inserted to proper hepatic artery. After the catheter placement confirmed by angiography, umbilical cord MSCs will be infused slowly in 20-30 minutes. Umbilical cord MSCs will be infused intravenously slowly in 30-60 minutes in the intravenous infusion group. The control group will receive conserved therapy. The levels of serum alanine aminotransferase (ALT), total bilirubin (TB), prothrombin time (PT), prealbumin(PA)and albumin (ALB) will be examined at re-transplantation, and 3 days to 2 years post-transplantation. The efficacy of umbilical cord MSCs transfusion will be investigated. The efficacy of different interventional therapies will also be compared.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-70 years.
• Imaging evidences of liver cirrhosis.
• Child-Plough score of 8 or more.
• Model for End-Stage Liver Disease score of 20 or more.

Exclusion Criteria:

• Liver tumor on ultrasonography, CT or MRI examination.
• Problems in organs other than liver (e.g. heart or lungs).
• History of moderate to severe hepatic encephalopathy or variceal bleeding.
• Imaging evidences of vascular thromboses.
• Coma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conserved Therapy	Drug: Conserved Therapy; Conserved Therapy
Experimental: Interventional Therapy; Patients with liver cirrhosis will be randomly divided into three groups. 1. Umbilical cord MSCs will be infused to patients using interventional method via hepatic artery for one group.2. Umbilical cord MSCs will be infused to patients intravenously for another group. The control group will receive conserved therapy. The efficacy of different interventional therapies will be compared.	Procedure: Hepatic artery infusion or Intravenous infusion; Patients with liver cirrhosis will be randomly divided into three groups. Umbilical cord MSCs will be infused to patients using interventional method via hepatic artery for one group. The catheter will be inserted to proper hepatic artery. After the catheter placement confirmed by angiography, umbilical cord MSCs will be infused slowly in 20-30 minutes. Umbilical cord MSCs will be infused intravenously slowly for 30-60 minutes in the intravenous infusion group. The control group will receive conserved therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	1 year
The level of serum alanine aminotransferase (ALT）	1 year
The level of serum total bilirubin (TB)	1 year
The level of serum prothrombin time (PT)	1 year
The level of serum prealbumin(PA)	1 year
The level of serum albumin (ALB)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	2 years
liver biopsy	2 years
The level of serum alanine aminotransferase (ALT）	2 years
The level of serum total bilirubin (TB)	2 years
The level of serum prothrombin time (PT)	2 years
The level of serum albumin (ALB)	2 years

Collaborators and Investigators

• Sponsor: Yufang Shi
• Collaborators: Soochow University
• Investigators: Principal Investigator: Yufang Shi, PhD,DVM, Chinese Academy of Sciences; Study Chair: Jianhe Gan, MD, the First Affiliated Hospital of Soochow University

Publications and helpful links

General Publications

• Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008 Feb 7;2(2):141-50. doi: 10.1016/j.stem.2007.11.014.
• Terai S, Ishikawa T, Omori K, Aoyama K, Marumoto Y, Urata Y, Yokoyama Y, Uchida K, Yamasaki T, Fujii Y, Okita K, Sakaida I. Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy. Stem Cells. 2006 Oct;24(10):2292-8. doi: 10.1634/stemcells.2005-0542. Epub 2006 Jun 15.
• Kharaziha P, Hellstrom PM, Noorinayer B, Farzaneh F, Aghajani K, Jafari F, Telkabadi M, Atashi A, Honardoost M, Zali MR, Soleimani M. Improvement of liver function in liver cirrhosis patients after autologous mesenchymal stem cell injection: a phase I-II clinical trial. Eur J Gastroenterol Hepatol. 2009 Oct;21(10):1199-205. doi: 10.1097/MEG.0b013e32832a1f6c.
• Dai LJ, Li HY, Guan LX, Ritchie G, Zhou JX. The therapeutic potential of bone marrow-derived mesenchymal stem cells on hepatic cirrhosis. Stem Cell Res. 2009 Jan;2(1):16-25. doi: 10.1016/j.scr.2008.07.005. Epub 2008 Aug 6.
• Abdel Aziz MT, Atta HM, Mahfouz S, Fouad HH, Roshdy NK, Ahmed HH, Rashed LA, Sabry D, Hassouna AA, Hasan NM. Therapeutic potential of bone marrow-derived mesenchymal stem cells on experimental liver fibrosis. Clin Biochem. 2007 Aug;40(12):893-9. doi: 10.1016/j.clinbiochem.2007.04.017. Epub 2007 May 3.
• Li C, Kong Y, Wang H, Wang S, Yu H, Liu X, Yang L, Jiang X, Li L, Li L. Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis. J Hepatol. 2009 Jun;50(6):1174-83. doi: 10.1016/j.jhep.2009.01.028. Epub 2009 Mar 29. Erratum In: J Hepatol. 2009 Nov;51(5):973.
• Kim TH, Kim JK, Shim W, Kim SY, Park TJ, Jung JY. Tracking of transplanted mesenchymal stem cells labeled with fluorescent magnetic nanoparticle in liver cirrhosis rat model with 3-T MRI. Magn Reson Imaging. 2010 Sep;28(7):1004-13. doi: 10.1016/j.mri.2010.03.047.
• Rabani V, Shahsavani M, Gharavi M, Piryaei A, Azhdari Z, Baharvand H. Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression. Cell Biol Int. 2010 Apr 27;34(6):601-5. doi: 10.1042/CBI20090386.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: October 25, 2010
• First Submitted That Met QC Criteria: November 2, 2010
• First Posted (Estimate): November 3, 2010

Study Record Updates

• Last Update Posted (Estimate): February 22, 2016
• Last Update Submitted That Met QC Criteria: February 19, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Mesenchymal stem cells; liver Cirrhosis; Hepatic artery infusion; Intravenous infusion
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: SIBS-IHS-20101010; 2010CB945600 (Other Grant/Funding Number: 2010CB945600-Chinese Ministry of Health)