Safety and Efficacy of Human Mesenchymal Stem Cells for Treatment of Liver Failure

Study Overview
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Brief Summary
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Liver failure (LF) is a dramatic clinical syndrome with massive necrosis of liver cells. and liver transplantation is the only available therapeutic option for patients suffering with this condition. However, lack of donors, surgical complications, rejection, and high cost are serious problems. Previous study showed that bone marrow derived mesenchymal stem cells (BM-MSCs) replace hepatocytes in injured liver, and effectively rescue experimental liver failure and contribute to liver regeneration. In this study, the patients with LF will undergo administration of human umbilical cord mesenchymal stem cells (UC-MSCs) via peripheral vein transfusion to evaluate the safty and efficacy of UC-MSCs treatment for these patients.

Detailed Description
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Liver failure (LF) is a severe life-threatening condition, and is a dramatic clinical syndrome with massive necrosis of liver cells, and liver transplantation is the only available therapeutic option for patients suffering with this condition. However, lack of donors, surgical complications, rejection, and high cost are serious problems. Since current therapeutic options for LF that is usually with extremely poor prognosis are still limited, recent studies indicate that mesenchymal stem cells (MSCs), due to their function in immune modulation and liver-damage repair, are of great therapeutic potential for this disease. Previous study showed that bone marrow derived mesenchymal stem cells (BM-MSCs) replace hepatocytes in injured liver, and effectively rescue experimental liver failure and contribute to liver regeneration.The purpose of this study is to investigate the safety and initial efficacy of human umbilical cord MSC (UC-MSCs) treatment for patients with LF. In this study, MSCs were isolated from umbilical cord and generated in appropriate growth medium. 50 LF patients with LF received i.v. transfusion of 0.5-1.0×106 cells/kg of MSCs as the treated group and other 20 LF patients with LF were transfused with placebo without MSCs as control group. All 70 of them received the routine management for liver failure. During the 2-year follow up, the evaluation of safty and efficacy will be undergone to help to establish innovative cell-based therapies for the treatment of diseases.

Official Title
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Phase Ⅰ/Ⅱ Study of Human Umbilical Cord Derived Mesenchymal Stem Cells (UC-MSCs) for Treatment of Liver Failure

Conditions
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Liver Failure, Mesenchymal Stem Cells

Intervention / Treatment
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* Drug: Conventional plus MSC treatment
* Drug: Conventional plus pacebo treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-70 years Liver failure Negative pregnancy test (female patients in fertile age) Written consent Exclusion Criteria: Hepatocellular carcinoma or other malignancies Severe problems in other vital organs(e.g.the heart,renal or lungs) Pregnant or lactating women Severe bacteria infection Anticipated with difficulty of follow-up observation Other candidates who are judged to be not applicable to this study by doctors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Conventional plus MSC treatment<br>Participants will receive conventional treatment plus a dose of MSC from day 0 through the week 12 study visit. Participants will then be followed until 2 years study visit | Drug: Conventional plus MSC treatment<br>* Participants received conventional treatment and taken i.v., once per 4 week, at a dose of 0.5*10E6 MSC/kg body for 12 weeks.<br>|
| Experimental: Conventional plus pacebo treatment<br>Participants will receive conventional plus placebo treatment from day 0 through the week 12 study visit. Participants will then be followed until 2 years study visit | Drug: Conventional plus pacebo treatment<br>* Participants received conventional treatment and taken i.v., once per 4 week, at 50 ml saline for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The levels of serum Total Protein and Albumin |  | 2 years after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The levels of serum Total Bilirubin and Direct Bilirubin |  | 2 years after treatment | 
| The levels of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Cholinesterase (CHE) |  | 2 years after treatment | 
| The level of alpha-fetoprotein (AFP) |  | 2 years after treatment | 
| The content of ascites |  | 2 years after treatment | 
| Survival rate and time |  | 2 years after treatment | 
| Body temperature, tetter and allergy |  | Between 0 to 24 hours after UC-MSCs transfusion | 
| The levels of Prothrombin Activity (PA) and Prothrombin Time (PT) |  | 2 years after treatment | 
| The score for Model for End-Stage Liver Disease |  | 2 years after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Failure, Mesenchymal Stem Cells, Model for End-Stage Liver Disease, Ascite, Serum Albumin