Introduction: Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) have applications in immunity and modulate immunological responses via T-cell suppression. We initiated a double-blind, randomized, dose-escalation trial of autologous MSCs (A-MSCs) in living donor kidney transplantation (Tp). These A-MSC donors have variable immunologic and health profiles that may impact stem cell activity and potency. MSCs require activation (“licensing”) to exert immunomodulation by an inflammatory environment. Transplant induction techniques, used to reduce inflammation and cytokines’ effect on allograft rejection and function, may interfere with licensing and potency of A-MSCs. MSCs secrete indoleamine-2, 3-dioxygenase (IDO), generated in response to immune activation, which has been proposed as a “potency” marker for MSC immunosuppressive activity. Baseline activity of inherently variable A-MSCs, and interaction of immune suppression regimes with infusion of A-MSC activity are unknown. Correlating MSC licensing with clinical activity is hypothesized by relative IDO presence, and that the transplant inflammatory environment sufficient for MSC licensing.
Methods: Participants (3:1) received MSCs (1 x 103/kg) or saline. A-BM-MSCs were harvested 90d pre-transplant, cultured, and infused on d0 +d4 with basiliximab +/- immune suppression.  Blood collected at d0 (pre-infusion), 0.5, 1, 3, 6, 12h, and 1, 2, 4, 14, 30, 60, 90, and 180d post-transplant was assessed by flow cytometry for CD8+ (cytotoxic T), CD4+ (helper T), Tregs, CD24+ B, Th1/2/17 status, and CD11C+ DC cell presence. IDO was measured by HPLC-MS/MS.  Serum IDO and Flow cytometry data were correlated with serology or biopsy up to two years post-transplant with the focus on rejection events.
Results: Four patients (pts) have received MSCs or saline after kidney-transplant. One pt had CMV infection and acute rejection ten-month post-transplant. Interestingly, Patient with acute rejection showed an up-regulation of serum IDO-1 as well as low levels of tryptophan which represent key indicators of inflammation compared to the other three patients that had no rejection episodes.
Conclusion: IDO presence is a novel assessment for variable activity and potency of MSCs in living-donor kidney transplantation and play an important role in immune status and acute rejection episodes.