BACKGROUNDSevere 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.METHODSWe 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.RESULTSSixteen 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 infusionCONCLUSIONTreatment 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 REGISTRATIONEudraCT 2016-004804-77.FUNDINGAIFA Ricerca Indipendente 2016-02364623.

Vivarelli, M., Colucci, M., Algeri, M., Zotta, F., Emma, F., L'Erario, I., Busutti, M., Rota, S., Capelli, C., Introna, M., Todeschini, M., Casiraghi, F., Perna, A., Peracchi, T., De Salvo, A., Rubis, N., Locatelli, F., Remuzzi, G., Ruggenenti, P., A phase I study of autologous mesenchymal stromal cells for severe steroid-dependent nephrotic syndrome, <<JCI INSIGHT>>, 2023; 8 (18): 1-13. [doi:10.1172/jci.insight.169424] [https://hdl.handle.net/10807/276683]

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

Locatelli, Franco
Conceptualization
;
2023

Abstract

BACKGROUNDSevere 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.METHODSWe 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.RESULTSSixteen 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 infusionCONCLUSIONTreatment 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 REGISTRATIONEudraCT 2016-004804-77.FUNDINGAIFA Ricerca Indipendente 2016-02364623.
2023
Inglese
Vivarelli, M., Colucci, M., Algeri, M., Zotta, F., Emma, F., L'Erario, I., Busutti, M., Rota, S., Capelli, C., Introna, M., Todeschini, M., Casiraghi, F., Perna, A., Peracchi, T., De Salvo, A., Rubis, N., Locatelli, F., Remuzzi, G., Ruggenenti, P., A phase I study of autologous mesenchymal stromal cells for severe steroid-dependent nephrotic syndrome, <<JCI INSIGHT>>, 2023; 8 (18): 1-13. [doi:10.1172/jci.insight.169424] [https://hdl.handle.net/10807/276683]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/276683
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