MSC Therapy in Liver Transplantation

Study Overview
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Brief Summary
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The general aim of the present study is to test a cell therapy with third-party allogeneic ex-vivo expanded MSCs as a strategy to induce tolerance in liver transplant recipients. MSCs will be prepared accordingly to established protocols , starting from diagnostic samples of bone marrow aspirates (2-5 mL) or using the remnants in the bag and filter at the end of the bone marrow infusions. From these samples, MSCs will be expanded in GMP approved facilities and used for the present study in patients undergoing liver transplantation.

Official Title
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THIRD-PARTY BONE MARROW-DERIVED MESENCHYMAL STROMAL CELLS TO INDUCE TOLERANCE IN LIVER TRANSPLANT RECIPIENTS

Conditions
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Liver Transplant Rejection

Intervention / Treatment
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* Biological: Mesenchymal Stromal Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For this study, the following inclusion criteria should be fulfilled before starting withdrawal of drugs after 1 year post-transplant: First liver transplant Capable of understanding the purpose and risk of the study Written informed consent Exclusion Criteria: Specific contraindication to MSC infusion Any clinical relevant condition that might affect study participation and/or study results Pregnant women and nursing mothers Unwillingness or inability to follow the study protocol in the investigator's opinion.

Ages Eligible for Study
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Minimum Age: 18 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal Stromal Cells (MSC)<br>A single intravenous infusion (1-2 millions of MSCs per kilogram body weight) of ex-vivo expanded third-party MSC (from healthy donors) will be performed in patients assigned to the MSC procedure in addition to the liver transplantation. | Biological: Mesenchymal Stromal Cells<br> <br> |
| No Intervention: No treatment.<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | At each visit overall clinical condition of the patient will be evaluated and any adverse event will be recorded. | Changes from baseline up to 120 month. | 
| Liver tissue mRNA level of Transferrin receptor CD71 (TFRC) and Hepcidin antimicrobial peptide (HAMP) genes |  | At 12 and 60 month. | 
| Circulating naive and memory T cell conts (CD45RA/CD45RO)(flow cytometry analysis) |  | Changes from baseline at 6 and 12 months after transplant, then every 6 months till the first 3 years after transplant and then yearly up to 120 month. | 
| T-cell function in mixed lymphocyte reaction |  | Changes from baseline at 6 and 12 months after transplant, then every 6 months till the first 3 years after transplant and then yearly up to 120 month. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stromal cells; liver transplantation; tolerance.