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. TRIAL REGISTRATION: EudraCT 2016-004804-77. FUNDING: AIFA Ricerca Indipendente 2016-02364623.