Evaluation of Stem Cell Therapy Effects on the Immune Response in Rheumatoid Arthritis Patients
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional
Phase: Phase 1

Summary: 
      1. Objectives: Evaluation of mesenchymal stem cell therapy effects on cellular and humoral
           immune responses in refractory rheumatoid arthritis (RA) patients.

        2. Design: This study has been performed as a phase 1 clinical trial.

        3. Setting and conduct: Autologous bone marrow derived mesenchymal stem cells were obtained
           by bone marrow aspiration and cultured in Minimum Essential Medium-Alpha (MEM-alpha) for
           4 weeks in standard clean room and then transfused to RA patients intravenously.

        4. Participant's major eligibility criteria is as follows: Ten refractory rheumatoid
           arthritis patients who show resistance to non biological Disease-modifying antirheumatic
           drugs (DMARDs) after 6 to 12 months have been enrolled in this study.

        5. Intervention: A single dose of intravenous autologous bone marrow derived mesenchymal
           stem cells have been administered into patients with resistance to non-biological
           DMARDs.

        6. Main outcome measures (variables): Finding of mesenchymal stem cell therapy effects on
           the cellular and humoral immune responses and evaluation of the effect of chemokines in
           homing of immune cells following the intervention.
    

Detailed description: 
      Refractory rheumatoid arthritis patients who met the inclusion/exclusion criteria have been
      selected. After signing informed consent form, autologous stem cells were obtained by bone
      marrow aspiration. Isolation and culture (3 to 4 weeks in MEM-alpha medium) of mesenchymal
      stem cells (MSCs) were performed in accredited good manufacturing practices (GMP) clean room.
      A panel of cluster of differentiation (CD) markers including CD105, CD166, CD44, CD45, CD90,
      and CD34 were checked for making sure about differentiation of cells into MSCs after 3-4
      weeks of cell culture. Viability of MSCs was checked by Trypan blue testing and all of the
      cultivations were negative for bacterial contamination. A single dose of 1000000 to 2000000
      mesenchymal stem cells/kg infused into patients intravenously. To prevent anaphylactic
      reactions, a single intravenous dose of hydrocortison (100 ml) and oral dimenhydrinate (10
      ml) were administered before MSCs infusion into patients. The effects of mesenchymal stem
      cells on the cellular and humoral immune responses and also the role of chemokines in homing
      of immune cells were studied at time points 1, 6 and 12 months after intravenous
      administration of MSCs in refractory rheumatoid arthritis.
    

Intervention name(s): Autologous mesenchymal stem cells
Intervention type(s): Biological
Intervention description(s): A single intravenous administration of autologous bone marrow derived mesenchymal stem cells(1000000 to 2000000 cells/Kg)
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Rheumatoid arthritis; Stem Cells; Cellular immunity; Humoral immunity; chemokines; homing of immune cells