Autologous Bone Marrow Stem Cells in Cirrhosis Patients

Study Overview
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Brief Summary
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Liver cirrhosis (LC) is the end stage of chronic liver disease. The liver transplantation is one of the only effective therapies available to such patients. However, lack of donors, surgical complications, rejection, and high cost are it's serious problems. The potential for stem cells in bone marrow (BM) to differentiate into hepatocytes cells was recently confirmed. Moreover, BMC transplantation has been performed to treat hematological diseases, and several clinical studies have applied BMC injection to induce regeneration of myocardium and blood vessels. In this study we will evaluate safety and feasibility of autologous bone marrow mono nuclear (BM-MNC) and enriched CD133+ hematopoietic stem cell transplantation through the portal vein in patients with decompensate cirrhosis.

Detailed Description
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BM (200 ml) will be harvested from the iliac crest according to standard procedures under general anesthesia and is collected in plastic bags containing anti coagulant. After precipitation of red blood cells, Low density mononuclear cells will be collected by centrifugation in Ficoll-Paque density gradient. For CD133+ cells separation the CliniMACS instrument will be used. Cells are injected via portal vein under sonography monitoring. After cell therapy, patients are followed up every week for 4 weeks, and laboratory data are analyzed for 24 weeks.

Official Title
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Autologous Transplantation of Bone Marrow Derived CD 133 Positive Stem Cell and Mono Nuclear Cell (MNC) Transplantation in Patients With Decompensate Cirrhosis: Randomized Clinical Trial

Conditions
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Stem Cell Transplantation, Cirrhosis

Intervention / Treatment
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* Biological: CD133
* Biological: BM-MNC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Liver biopsy showing histological Cirrhosis, grade B or C (Child-Pugh score) Alkaline phosphatase between 2 X to 3X normal value liver Cirrhosis in Sonography study Incomplete response to UDCA after 6 months of treatment. Negative pregnancy test (female patients in fertile age) written consent Exclusion Criteria: Presence of active hepatic encephalopathy Refractory ascites Evidences of active autoimmune liver disease (e.g. gamma globulin of more than 2 times of upper limit of normal, and ALT > 3 times normal in patients with autoimmune hepatitis) Hepatocellular carcinoma or other malignancies sepsis Presence of significant extrahepatic biliary disease (e.g. CBD stone, PSC, etc.) HIV, HBV or HCV infection Cardiac, renal or respiratory failure Active thrombosis of the portal or hepatic veins INR>2

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Biological: CD133<br>* portal vein infusion of CD133+ cells<br>|
| Experimental: 2<br> | Biological: BM-MNC<br>* portal vein infusion of BM-MNC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver function test |  | 6 months | 
| MELD score |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cirrhosis mortality |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous Bone marrow stem cells, Cirrhosis