A Perspective Multicenter Controlled Study On Application Of Mesenchymal Stem Cell(MSC) To Prevent Rejection After Renal Transplantation By Donation After Cardiac Death

Study Overview
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Brief Summary
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Although donation after cardiac death(DCD) is the major source of renal transplantation in China, high incidence rate of rejection and delayed graft function(DGF) is existing due to the prolonged ischemia time. According to the previous single center study, mesenchymal stem cell (MSC) had an effect to prevent rejection and DGF after renal transplantation, but there was no perspective multicenter controlled study to confirm it. This perspective multicenter controlled study will focus on clarifying the key role of MSC applied via renal arterial or peripheral vein injection, to reduce the rejection and DGF after renal transplantation. The investigators have established GMP workshop and solid research foundation of transplant rejection. This study will provide a new reasonable way for immune induction of renal transplantation by DCD.

Conditions
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Disorder Related to Renal Transplantation, Renal Transplant Rejection

Intervention / Treatment
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* Biological: mesenchymal stem cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study on prevention of MSC to rejection after transplantation Age between 18-60 years having the indication of renal transplantation having no absolute contraindication renal transplantation by donation after citizen death the first time to receive renal transplantation signed informed consent Study on treatment of MSC to rejection after transplantation renal transplantation by donation after citizen death BPAR having no contraindication of renal biopsy signed informed consent Exclusion Criteria: loss to follow-up serious adverse events

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iv of BMSC to prevent rejection<br>Routine treatment protocol(ATG 50mg*3;MP 2.0g to Pred 30mg,then maintaining 5mg qd;MMF 1.0 bid from the first day after op,then maintaining 1-1.5g/d;Plus CNI from the third day after op)+BMSC iv(2*10^6cell/kg, 48h before op) | Biological: mesenchymal stem cell<br> <br> |
| No Intervention: routine treatment protocol to prevent rejection<br>Routine treatment protocol(ATG 50mg*3;MP 2.0g to Pred 30mg,then maintaining 5mg qd;MMF 1.0 bid from the first day after op,then maintaining 1-1.5g/d;Plus CNI from the third day after op) | |
| Experimental: ia and iv of MSC to prevent rejection<br>Routine treatment protocol(ATG 50mg*3;MP 2.0g to Pred 30mg,then maintaining 5mg qd;MMF 1.0 bid from the first day after op,then maintaining 1-1.5g/d;Plus CNI from the third day after op)+BMSC (iv 2*10^6cell/kg + ia 5*10^6cell, 48h before op) | Biological: mesenchymal stem cell<br> <br> |
| No Intervention: routine treatment to prevent rejection<br>Routine treatment protocol(ATG 50mg*3;MP 2.0g to Pred 30mg,then maintaining 5mg qd;MMF 1.0 bid from the first day after op,then maintaining 1-1.5g/d;Plus CNI from the third day after op) | |
| Experimental: Routine CMR treatment plus MSC to prevent CMR<br>Routine CMR treatment protocol(MP as first line approach, ATG as second line approach,ATG be used to treat BPAR in 1 week after op)+MSC( iv 2*10^6cell/kg at d1,d7) | Biological: mesenchymal stem cell<br> <br> |
| No Intervention: Routine CMR treatment to prevent CMR<br>Routine CMR treatment protocol(MP as first line approach, ATG as second line approach,ATG be used to treat BPAR in 1 week after op) | |
| Experimental: Routine AMR treatment plus MSC to prevent AMR<br>Routine AMR treatment protocol(plasma exchange and IVIG as first line approach, anti-CD20 monoclonal antibody as second line approach)+MSC( iv 2*10^6cell/kg at d1,d7) | Biological: mesenchymal stem cell<br> <br> |
| No Intervention: Routine AMR treatment to prevent AMR<br>Routine AMR treatment protocol(plasma exchange and IVIG as first line approach, anti-CD20 monoclonal antibody as second line approach) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers of participants enrolled into the MSC group and control group | 80-100 cases will be enrolled to the group. | up to one year | 
| Incident rates of BPAR and DGF after renal transplantation with MSC prevention before operation | Cases enrolled into the group will be monitored renal function,renal biopsy and other opportunistic infection.The incident rates of DGF and BPAR will be calculated and compare with the control group. | up to one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal transplantation, mesenchymal stem cell, Transplantation Rejection, donation after cardiac death