Therapeutic Strategy and the Role of Mesenchymal Stromal Cells for ABO Incompatible Liver Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to determine whether MSCs are safe and effective in reducing the primary nonfunction (PNF), acute rejection and Ischemic-type Biliary Lesions (ITBLs) morbidity in ABO-incompatible Liver Transplantation.

Detailed Description
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ABO incompatible liver transplantations is considered to be a rescue option in emergency transplantation.The A、B antibodies to grafts bind to the graft endothelium and activate complement, which attracts and activates neutrophils and platelets and increases the permeability of the endothelium. The neutrophils exude, the platelets aggregate, and the small vessels of the graft get thrombosed, resulting in ischemic damage,leading nonfunction grafts.In addition, if the A、 B antibodies remain high level, it can lead to acute humoral immune rejection. A lot of research confirmed that the ABO incompatible is a risk factor of postoperative short- and long-term survival. And mesenchymal stromal cells (MSCs) are characterized by the properties of immunosuppressive and regenerative properties, which make MSCs great attractive in treating immunological diseases (including transplant rejection) and organ/tissue ischemic injury. So we conduct this clinical study,to confirm the effect of MSCs in ABO incompatible liver transplantation by comparing the incidence of primary nonfunction, acute rejection, biliary complications and survival rates.

Official Title
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MSC for ABO Incompatible Liver Transplantation

Conditions
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Liver Transplantation

Intervention / Treatment
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* Biological: Mesenchymal Stem Cells(MSCs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First liver transplantation with a ABO-incompatible graft(B→A，AB→A，A→B，AB→B，A→O，B→O，AB→O). Ages of 18 or older. Patients receive liver transplantation due to benign end stage liver disease. Patients or legal agent must be able to give informed consent. Exclusion Criteria: Second or combined organ transplant recipient. Combined transplantations such as simultaneous liver/kidney transplants Malignant disease. Uncontrol bacterial, fungal, viral or parasitic infection. Withdraw or unable to finish the follow-up. Unwilling to sign informed consent.

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The MSCs group<br>The group of patients receive allogeneic MSCs therapies. | Biological: Mesenchymal Stem Cells(MSCs)<br>* Six doses of 1*10^6/kg body weight MSCs are given, intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: one year graft survival rate |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the rate of acute rejection |  | one year | 
| the rate of ischemic-type biliary lesions |  | one year | 
| safety: rate of (serious) adverse events in the study population | adverse events include: allergic reaction, prothrombotic effects, opportunistic infections and malignancy | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stromal cells, Liver Transplantation, ABO blood group