ABMSC Infusion Through Hepatic Artery in Portal Hypertension Surgery for the Treatment of Liver Cirrhosis

NCT ID: NCT01560845

Last Updated: 2012-03-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2014-06-30

Brief Summary

In recent years, the safety and efficacy of autologous bone marrow stem cells infusion (ABMSCi) therapy were confirmed. The investigators attempted to infuse autologous bone marrow stem cells (ABMSC) through inserting a catheter into right gastric artery as far as proper hepatic artery after finishing open abdominal portal hypertension surgery. The present study was designed to treat bleeding from esophageal varices and hypersplenism and hopefully to improve the liver function as well.

Detailed Description

1. ABMSC mobilization and harvest

• For harvesting more ABMSC, ABMSC mobilization was induced by rhG-CSF (Gran○R), administered subcutaneously at a dose of 300μg daily for three consecutive days before open abdominal portal hypertension surgery.
• Bone marrow (160-200ml) of the patients was harvested from both posterior superior iliac according to standard procedures under local anaesthesia and was collected in a plastic bag containing heparin.

2. Open abdominal portal hypertension surgery

• Immediately after the harvest of ABMSC, the modified Sugiura procedure was performed for the patients who were assigned to the study group. The same surgical procedure was also performed for the control group (without harvest of ABMSC and ABMSC infusion).

3. ABMSC separation and infusion

• While performing the portal hypertension surgery, ABMSC was separated and purified in a class 10,000 clean laboratory. After fat and bony particles were removed by filtration, collected cells were moved to a cell-processing device. We used the reagent kit ([Patent Number] ZL 2006 1 0106875.5; [Number of Criteria Applicable] YZB/NING YIN 0008-2008; [Researcher and Developer] Wealthlin Science & Technology Inc., Canada; [Producer] Ningxia Zhonglianda Biotech Co., Ltd.). 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 was measured by an automated complete blood count instrument and flow cytometry analysis. The number of mononuclear cells was counted manually under a microscope by Wright-Giemsa stain method. CD34 positive cells were determined by flow cytometry analysis.
• The time of ABMSC separation and purification was 2.5-3 hours which had to be completed before the conclusion of portal hypertension surgery (3-3.5 hours). ABMSC was added to 10 ml saline and well mixed by shaking the vial gently. Before incision closure, the right gastric artery or right gastroepiploic artery was selected and a catheter was inserted. The catheter was 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 or right gastroepiploic artery (central venous catheterization, REF product NO.ES-04218, Arrow International, Inc.). The mixture of saline and AMBC was infused into hepatic artery at uniform speed for about two minutes. The catheter was removed after the ABMSCi. The puncture point of the right gastric artery was repaired using blood vessel suture or transfixed.

4. 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 analyses were performed using the SPSS 15.0 statistical package (SPSS Inc., Chicago, IL, USA). All statistical analyses were based on two-tailed hypothesis tests with a significance level of p< 0.05.

Conditions

Liver Cirrhosis; Portal Hypertension; Hepatic Decompensation; Surgery

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ABMSCi plus surgery group

Autologous bone marrow stem cells infusion through hepatic artery in open abdominal portal hypertension surgery

Group Type: EXPERIMENTAL

Autologous bone marrow stem cells infusion （ABMSCi） plus abdominal portal hypertension surgery

Intervention Type: PROCEDURE

Immediately after the harvest of ABMSC, the modified Sugiura procedure was performed for the patients who were assigned to the study group. The time of ABMSC separation and purification was 2.5-3 hours which had to be completed before the conclusion of portal hypertension surgery (3-3.5 hours). ABMSC was infused into proper hepatic artery through right gastric artery during the portal hypertension surgery

portal hypertension surgery group

only portal hypertension surgery for this group patients

Group Type: NO_INTERVENTION

open abdominal portal hypertension surgery

Intervention Type: PROCEDURE

the modified Sugiura procedure was performed for the patients

Interventions

Autologous bone marrow stem cells infusion （ABMSCi） plus abdominal portal hypertension surgery

Immediately after the harvest of ABMSC, the modified Sugiura procedure was performed for the patients who were assigned to the study group. The time of ABMSC separation and purification was 2.5-3 hours which had to be completed before the conclusion of portal hypertension surgery (3-3.5 hours). ABMSC was infused into proper hepatic artery through right gastric artery during the portal hypertension surgery

Intervention Type: PROCEDURE

open abdominal portal hypertension surgery

the modified Sugiura procedure was performed for the patients

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Advanced liver cirrhosis after hepatitis B resulted in bleeding from esophageal varices and hypersplenism, and needed open abdominal portal hypertension surgery;

2. Endoscopy evidence of showing severe gastric and esophageal varices;

3. Severe hypersplenism （white blood cells (WBC) <3×109/L and platelet (PLT) <100×109/L）;

4. Active bone marrow hyperplasia showed by bone marrow biopsy before surgery;

5. Age between 18 and 60 years;

6. Plasma albumin <35g/L, or mild ascites;

Exclusion Criteria

1. Enlisted for liver transplantation

2. Diagnosis of hepatocellular carcinoma or other cancers

3. Other severe medical disease, and acute infection.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wenzhou Medical University

OTHER

Sponsor Role: lead

Responsible Party

Qiqiang Zeng

the secretary-general of stem cell research center of Wenzhou Medical College

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

qiyu zhang, MD

Role: STUDY_CHAIR

First Affiliated Hospital of Wenzhou Medical University

Locations

the First Affiliated Hospital of Wenzhou Medical College

Wenzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

qiqiang zeng, MD

Role: CONTACT

zengqiqiangwz@163.com

86-0577-88069307

Facility Contacts

qiqiang zeng, MD

Role: primary

zengqiqiangwz@163.com

86-0577-88069307

References

am Esch JS, Schmelzle M, Furst G, Robson SC, Krieg A, Duhme C, Tustas RY, Alexander A, Klein HM, Topp SA, Bode JG, Haussinger D, Eisenberger CF, Knoefel WT. Infusion of CD133+ bone marrow-derived stem cells after selective portal vein embolization enhances functional hepatic reserves after extended right hepatectomy: a retrospective single-center study. Ann Surg. 2012 Jan;255(1):79-85. doi: 10.1097/SLA.0b013e31823d7d08.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 21608000 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 16778155 (View on PubMed)

Other Identifiers

WZMC1-10-1

Identifier Type: -

Identifier Source: org_study_id