Abstract
Aim: To investigate the effectiveness and timing of the immunomodulatory response produced by mesenchymal stromal cells (MSCs) in a rat model of allogeneic kidney transplantation. Methods:To study the immunologic/immunosupressor effects of MSCs (donor), Lewis rats received an allogeneic kidney from Wistar rats. The infusion pattern of MSCs was determined in a previous experimental design where naïve rats were injected with 106cells and the principal cellular blood subpopulations were analyzed each 24 h.Rats were randomized into the four groups listed below and followed for 21 days. 1. NT, in which rats received infusion of PBS (n =7) 2. CsA, in which rats received a single daily dose of 5 mg/kg cyclosporine by oral gavages for 21 days (n =7) 3. MSC4, in which rats received two infusion of MSCs (106cells), Day -4 before renal transplantation and 1 hour after the surgery (n = 5) 4. MSC7, in which rats received two infusion of MSCs (106cells), Day -7 before renal transplantation and 1 hour after the surgery (n = 5). To study the principal cellular blood subpopulations and the renal function, samples were collected before the surgery, on day 7 post-transplant, and on the day of sacrifice. Results: Analyzing the three major subpopulations of lymphocytes in peripheral blood (T cells, B cells and NK cells), we observed that both MSC treatments decrease the percentage of the three lymphocyte subpopulations at 7 days post-transplantation. But the MSC7 group showed a percentage of lymphocytes similar to the CsA group. The renal function, measured by creatinine clearance, in the MSC7 group was significantly lower than the MSC4 and NT. The MSC7 group had significantly increased the survival respect to MSC4 and NT groups. Conclusions: MSC have a beneficial effect on the immune system of transplanted rats which improved graft function. However, the infusion pattern of MSCs plays a crucial role in the immune system modulation.
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