A phase I study of autologous mesenchymal stromal cells for severe steroid-dependent nephrotic syndrome

BACKGROUND. Severe forms of idiopathic nephrotic syndrome (INS) require prolonged immunosuppressive therapies and repeated courses of high-dose glucocorticoids. Mesenchymal stromal cells (MSCs) have promising immunomodulatory properties that may be employed therapeutically to reduce patient exposure to medications and their side effects.METHODS. We performed a phase I open-label trial assessing safety and feasibility of autologous bone marrow-derived MSCs (BM-MSCs) in children and young adults with severe forms of steroid -dependent nephrotic syndrome. Following autologous BM-MSC preparation and infusion, oral immunosuppression was tapered. Safety, efficacy, and immunomodulatory effects in vivo were monitored for 12 months.RESULTS. Sixteen patients (10 children, 6 adults) were treated. Adverse events were limited and not related to BM-MSC infusions. All patients relapsed during follow-up, but in the 10 treated children, time to first relapse was delayed (P = 0.02) and number of relapses was reduced (P = 0.002) after BM-MSC infusion, compared with the previous 12 months. Cumulative prednisone dose was also reduced at 12 months compared with baseline (P < 0.05). No treatment benefit was observed in adults. In children, despite tapering of immunosuppression, clinical benefit was mirrored by a significant reduction in total CD19+, mature, and memory B cells and an increase in regulatory T cells in vivo up to 3-6 months following BM-MSC infusion.CONCLUSION. Treatment with autologous BM-MSCs is feasible and safely reduces relapses and immunosuppression at 12 months in children with severe steroid-dependent INS. Immunomodulatory studies suggest that repeating MSC infusions at 3-6 months may sustain benefit.

Automated summary

This study evaluated the therapeutic effects and immunomodulatory properties of autologous bone marrow-derived MSCs in children and young adults with severe steroid-dependent nephrotic syndrome. The results showed that BM-MSC infusion delayed the time to first relapse, reduced the number of relapses, and decreased the use of immunosuppressive drugs in treated children. No treatment benefit was observed in adults. Moreover, immunomodulatory studies suggested that repeating MSC infusions at 3-6 months may sustain the therapeutic benefits.