Stem Cell Research & Therapy (Aug 2022)

First clinical application of cord blood mesenchymal stromal cells in children with multi-drug resistant nephrotic syndrome

  • William Morello,
  • Silvia Budelli,
  • Daniel Ari Bernstein,
  • Tiziana Montemurro,
  • Elisa Montelatici,
  • Cristiana Lavazza,
  • Luciana Ghio,
  • Alberto Edefonti,
  • Licia Peruzzi,
  • Daniela Molino,
  • Elisa Benetti,
  • Bruno Gianoglio,
  • Florian Mehmeti,
  • Laura Catenacci,
  • Jessica Rotella,
  • Chiara Tamburello,
  • Antonia Moretta,
  • Lorenza Lazzari,
  • Rosaria Giordano,
  • Daniele Prati,
  • Giovanni Montini

DOI
https://doi.org/10.1186/s13287-022-03112-7
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 9

Abstract

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Abstract Background and objectives Children with multi-drug resistant idiopathic nephrotic syndrome (MDR-INS) usually progress to end-stage kidney disease with a consistent risk of disease recurrence after transplantation. New therapeutic options are needed for these patients. Mesenchymal stromal cells (MSCs) are multipotential non-hematopoietic cells with several immunomodulatory properties and growing clinical applications. Cord blood-derived MSC have peculiar anti-inflammatory and immunosuppressive properties. We aimed at assessing safety and efficacy of cord-blood-derived MSCs (CB-MSCs) in children with MDR-INS. Design, setting, participants Prospective, open-label, single arm phase I–II pilot study. Pediatric patients with MDR-INS, resistant to at least two lines of therapy, were enrolled. Allogenic CB-MSCs were administered intravenously on days 0, 14, and 21 at a dose of 1.5 × 106 cells/kg. Patients were followed for at least 12 months. The primary outcomes were safety and toxicity. The secondary outcome was remission at 12 months evaluated by urinary protein/urinary creatinine ratio (uPr/uCr). Circulating regulatory T cells (Tregs) were monitored. Results Eleven pediatric patients with MDR-INS (10 females, median age 13 years) resistant to a median of 3 previous lines of therapy were enrolled. All patients completed the CB-MSC infusion schedule. No patient experienced any infusion-related adverse event or toxicity. Nine patients were assessable for efficacy. At the 12 months follow-up after the treatment, the median uPr/uCr did not change significantly from baseline (8.13 vs. 9.07; p = 0.98), while 3 patients were in partial or complete remission. A lower baseline uPr/uCr was a predictor of remission (2.55 vs. 8.74; p = 0.0238). Tregs count was not associated with CB-MSCs therapy. Conclusions CB-MSCs are safe and may have a role in the immunosuppressive therapy of pediatric patients with MDR-INS. This preliminary experience paves the way toward further phase II studies addressing MSC efficacy in immune-mediated kidney diseases.

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