Autologous Bone Marrow Stem Cells Infusion for the Treatment of Liver Diseases.

Study Overview
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Brief Summary
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This study evaluates the effect of autologous bone marrow stem cells infusion (ABMSCi) therapy for liver diseases.Treatment group will receive ABMSCi and drugs therapy ,while control group will only receive drugs therapy.

Detailed Description
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Autologous bone marrow stem cells (ABMSC) mobilization and harvest For harvesting more ABMSC, ABMSC mobilization is induced by recombinant human granulocyte colony stimulating factor (rhGCSF,Gran○R), administered subcutaneously at a dose of 300μg daily for three consecutive days before bone marrow puncture. Bone marrow (160-200ml) of the patients is harvested from both posterior superior iliacs according to standard procedures under local anaesthesia and is collected in a plastic bag containing heparin. Both treatment group and control group receive drugs therapy. ABMSC separation and infusion ABMSC is separated and purified in a class 10,000 clean laboratory. After fat and bony particles are removed by filtration, collected cells are moved to a cell-processing device. The reagents adopt the method of negative cells collection. Take the cells which intended to remove as target cells, and carry out the removal step-by-step. On the basis of this method, red blood cells, blood platelets, blood plasma will be completely removed with part of white cells and lymphocytes being remarkably removed as well while all the stem cells / progenitor cells are being well retained. The nucleated cell (white blood cell) count of final ABMSC is measured by an automated complete blood count instrument and flow cytometry analysis. The number of mononuclear cells is counted manually under a microscope by Wright-Giemsa stain method. Cell differentiation factor 34(CD34) positive cells were determined by flow cytometry analysis. The time of ABMSC separation and purification is 2.5-3 hours. ABMSC is added to 10 ml saline and well mixed by shaking the vial gently. The catheter is pushed to reach the proper hepatic artery. The diameter of the catheter is 1.4mm, it is thin enough to easily been inserted to right gastric artery . The mixture of saline and ABMSC is infused into proper hepatic artery at uniform speed for about two minutes. The catheter is removed after the ABMSCi. Statistical analysis - Categorical data are presented as absolute values and percentages, whereas continuous data are summarized as mean and Standard Deviation. Statistical analysis was performed using t-test for paired or unpaired samples. Time courses of measurements of liver function parameters were analyzed by repeated-measures ANOVA. The analysis is performed using the Statistic Package for Social Science (SPSS). All statistical analysis is based on two-tailed hypothesis tests with a significance level of p< 0.05.

Official Title
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Autologous Bone Marrow Stem Cells Infusion for the Treatment of Liver Diseases.

Conditions
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Liver Diseases

Intervention / Treatment
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* Procedure: Autologous bone marrow stem cells infusion
* Drug: drugs such as Ursodeoxycholic Acid tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Definite liver diseases (such as viral hepatitis, autoimmune liver diseases, fatty liver diseases, ect); Active bone marrow hyperplasia showed by bone marrow biopsy before ABMSCi; Age between 18 and 60 years; Abnormal liver function. Exclusion Criteria: Enlisted for liver transplantation Diagnosis of hepatocellular carcinoma or other cancers Other severe medical disease, and acute infection pregnant or nursing females,co-infections with HIV ,serious bacterial infection other vital organ or system dysfunction with severe complications of liver cirrhosis hematological disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group: ABMSCi & drugs<br>ABMSCi: Autologous bone marrow stem cells infusion drugs such as Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally | Procedure: Autologous bone marrow stem cells infusion<br>* Autologous bone marrow stem cells are infused into proper hepatic artery<br>* Other names: ABMSCi;Drug: drugs such as Ursodeoxycholic Acid tablets<br>* Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally<br>* Other names: UDCA;|
| Active Comparator: control group: drugs<br>drugs such as Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally | Drug: drugs such as Ursodeoxycholic Acid tablets<br>* Ursodeoxycholic Acid tablets(UDCA), each time 150 mg, three times a day orally<br>* Other names: UDCA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline alanine aminotransferase at 6 months | alanine aminotransferase (ALT) | baseline and 6 months after treatment | 
| Change from baseline aspartate aminotransferase at 6 months | aspartate aminotransferase (AST) | baseline and 6 months after treatment | 
| Change from baseline total bilirubin at 6 months | total bilirubin (TBil) | baseline and 6 months after treatment | 
| Change from baseline direct bilirubin at 6 months | direct bilirubin (DBil) | baseline and 6 months after treatment | 
| Change from baseline total bile acid at 6 months | total bile acid (TBA) | baseline and 6 months after treatment | 
| Change from baseline albumin at 6 months | albumin (ALB) | baseline and 6 months after treatment | 
| Change from baseline prothrombin time at 6 months | prothrombin time (PT), | baseline and 6 months after treatment | 
| Change from baseline international normalized ratio at 6 months | international normalized ratio (INR) | baseline and 6 months after treatment | 
| Change from baseline white blood cell at 6 months | white blood cell (WBC) | baseline and 6 months after treatment | 
| Change from baseline platelet at 6 months | platelet (PLT) | baseline and 6 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline liver density at 6 months | Low density, medium density, high density tested by abdominal B ultrasound/CT/MRI | baseline and 6 months after treatment | 
| Change from baseline liver size at 6 months | Enlarged size, normal size, shrunken size tested by abdominal B ultrasound/CT/MRI | baseline and 6 months after treatment | 
| Change from baseline spleen thickness at 6 months | tested by abdominal B ultrasound/CT/MRI | baseline and 6 months after treatment | 
| Incidence of adverse events that are related to treatment | Postoperative pyrexia, infection, liver cirrhosis, ascites, upper gastrointestinal hemorrhage, malignant tumors of liver and other organs | baseline and 6 months after treatment | 
| Number of participants that survive without developing disease |  | 12 months after treatment | 
| Number of participants that survive with developing disease |  | 12 months after treatment | 
| Number of participants that die after treatment |  | 12 months after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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liver diseases, Bone Marrow Cell Transplantation