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

• Published in: JCI insight 2023-09, Vol.8 (18)
• Main Authors: Vivarelli, Marina, Colucci, Manuela, Algeri, Mattia, Zotta, Federica, Emma, Francesco, L'Erario, Ines, Busutti, Marco, Rota, Stefano, Capelli, Chiara, Introna, Martino, Todeschini, Marta, Casiraghi, Federica, Perna, Annalisa, Peracchi, Tobia, De Salvo, Andrea, Rubis, Nadia, Locatelli, Franco, Remuzzi, Giuseppe, Ruggenenti, Piero
• Format: Article
• Language: English
• Subjects: Child; Clinical Medicine; Clinical trials; Glucocorticoids - therapeutic use; Humans; Immunosuppression Therapy; Mesenchymal Stem Cells; Nephrology; Nephrotic Syndrome - therapy; Recurrence; Young Adult
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.169424

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.