Journal Article

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

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

2022

Overview

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 × 10 6 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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Advanced therapy medical products / Antigens / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Care and treatment / Cell Biology / Children / Children's furniture / Chronic kidney failure / Clinical trials / Cord blood / Cord-blood-derived mesenchymal stromal cells / Creatinine / Diseases / Drug resistance / End-stage renal disease / Flow cytometry / Good Manufacturing Practice / Graft versus host disease / Health aspects / Idiopathic nephrotic syndrome / Immunology / Immunomodulation / Immunoregulation / Immunosuppressive agents / Immunotherapy / Inflammation / Kidney diseases / Laboratories / Life Sciences / Lymphocytes T / Manufacturing / Medical research / Medicine, Experimental / Mesenchymal stem cells / Mesenchymal stromal cells / Mesenchyme / Multi-drug resistant nephrotic syndrome / Multidrug resistance / Nephrotic syndrome / Patients / Pediatrics / Regenerative Medicine/Tissue Engineering / Relapse / Remission / Remission (Medicine) / Risk assessment / Stem Cells / Steroids / Stromal cells / T cells / Technology application / Toxicity / Transplantation