Mesenchymal Stromal Cells in Kidney Transplant Recipients

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 autologous ex-vivo expanded mesenchymal stromal cells (MSCs) as a strategy to induce tolerance in living-donor kidney transplant recipients. MSCs will be prepared accordingly to established protocols, starting from bone marrow explants of living-donor kidney transplant recipients obtained 3-4 months before kidney transplant. From these samples, MSCs will be expanded in Good Manufacturing Practice (GMP) approved facilities and used for the present study in patients undergoing kidney transplantation.

Official Title
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Autologous Mesenchymal Stromal Cells to Induce Tolerance in Living-donor Kidney Transplant Recipients

Conditions
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Kidney 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: Male and female patients; Aged 18 or older; Living-donor (related and unrelated, spouse/husband) kidney transplant recipients; Non-Human Leukocyte Antigen (HLA) identical with the donor (one or two haplotype mismatches); First kidney transplant; Capable of understanding the purpose and risk of the study; Written informed consent. Exclusion Criteria: MSC donor positive for HIV-1, HIV-2, hepatitis B virus (HBV),hepatitis C virus (HCV), syphilis; 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 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mesenchymal Stromal Cells<br>A single intravenous infusion of ex-vivo expanded autologous MSCs will be performed in patients in addition to the living-donor kidney transplantation. 2x10 elevated to sxth power MSCs per kilogram body weight previously isolated from the same recipient will be infused intravenously the day before the kidney transplant procedure. | Biological: Mesenchymal Stromal Cells<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating naïve and memory T cell count (CD45RA/CD45RO) (flow cytometry analysis). |  | Changes from baseline at 6 and 12 months after transplant. | 
| T-cell function by ELISPOT assay in mixed lymphocyte reaction. |  | Changes from baseline at 6 and 12 months after transplant. | 
| Number of adverse events. | At each visit the overall clinical condition of the patient will be evaluated and any adverse event will be recorded. | Changes from baseline up to 48 months. | 
| Circulating regulatory T cell count. |  | Changes from baseline at 6 and 12 months after transplant. | 
| Urinary FOXP3 mRNA expression evaluated by real time quantitative PCR. |  | Changes from baseline at 6 and 12 months after transplant. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesenchymal stromal cells, Kidney transplantation, Tolerance