Mesenchymal Stem Cells and Subclinical Rejection
Condition: Organ Transplantation
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of the study is to test the safety and feasibility of autologous mesenchymal stem
      cell therapy in HLA-DR mismatched patients with subclinical rejection and or an increase in
      IF?TA in the renal biopsy 4 weeks or 6 months after renal transplantation.
    

Detailed description: 
      Kidney transplantation has improved survival and quality of life for patients with end-stage
      organ failure. Despite dramatic improvements in short-term survival, long-term survival of
      renal allografts has changed little during the past decade. Recently, it has been
      demonstrated that chronic lesions originate already very early after transplantation and that
      subclinical rejection (SCR) in protocol biopsies is a risk factor for late graft loss.
      However the efficacy of high-dose corticosteroids and other therapies for the treatment of
      SCR have been shown to be inadequate. Thus, despite the availability of a range of available
      medications there remains a need for therapeutic alternatives because patients may not
      respond to existing therapeutic choices, they do not show an improvement of the fibrosis
      reaction or an effect on long term survival, or they may develop immunosuppression induced
      serious (sometimes fatal) side effects and toxicities.

      In recent years it has become evident that bone marrow (BM) derived mesenchymal stem cells
      have potent immunomodulatory effects. MSCs are pluripotent cells that can differentiate into
      several mesenchymal tissues, including fibroblasts, osteoblasts, adipocytes and chondrocyte
      progenitors. MSCs have potent immunosuppressive effects on T and B cells in vitro and in
      animal models of chronic inflammation. Encouraging results have been obtained in patients
      with steroid resistant acute and severe Graft versus Host Disease (GvHD). The investigators
      hypothesize that infusion of MSCs may similarly provide a novel treatment option in the
      treatment of patients with allograft rejection with less side effects than existing
      immunosuppressive therapies.This study will evaluate the safety and feasibility of MSC
      therapy in renal recipients.

      In total 15 de novo renal recipients of 2 HLA-DR mismatched living donors, men and women,
      18-65 years of age, will be recruited from the renal transplant clinics of the LUMC. Only
      patients with SCR abd or an increase in IF/TA in the protocol biopsy 4 weeks or 6 months
      after transplantation will receive MSC infusions. MSCs from patients without SCR in their
      biopsy will be only used for feasibility and function studies (as described earlier).
      Subjects will receive two doses of 1 x 10.6 MSCs per kilogram body weight, intravenously, 7
      days apart. The investigators will investigate safety of MSC therapy by assessing the rate of
      (serious) adverse events in the study population using the World Health Organization (WHO)
      criteria. Feasibility will be obtained by determining the number of expanded MSCs in relation
      to the amount of BM collected, number of passages required and time to reach study target
      doses.
    

Intervention name(s): Mesenchymal stem cell infusion
Intervention type(s): Procedure
Intervention description(s): MSC infusion: two doses of 1-2x106 MSCs per kilogram body weight, intravenously, 7 days apart.
Other intervention name(s): Bone marrow derived mesenchymal stem cells.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Mesenchymal stem cells; Allograft rejection; Subclinical rejection