JCI Insight (Sep 2023)

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

  • Marina Vivarelli,
  • Manuela Colucci,
  • Mattia Algeri,
  • Federica Zotta,
  • Francesco Emma,
  • Ines L’Erario,
  • Marco Busutti,
  • Stefano Rota,
  • Chiara Capelli,
  • Martino Introna,
  • Marta Todeschini,
  • Federica Casiraghi,
  • Annalisa Perna,
  • Tobia Peracchi,
  • Andrea De Salvo,
  • Nadia Rubis,
  • Franco Locatelli,
  • Giuseppe Remuzzi,
  • Piero Ruggenenti

Journal volume & issue
Vol. 8, no. 18

Abstract

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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 infusionCONCLUSION 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.

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