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

Autor: Morello W; Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy., Budelli S; Laboratory of Regenerative Medicine, Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy., Bernstein DA; Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy., Montemurro T; Laboratory of Regenerative Medicine, Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy., Montelatici E; Laboratory of Regenerative Medicine, Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy., Lavazza C; Laboratory of Regenerative Medicine, Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy., Ghio L; Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy., Edefonti A; Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy., Peruzzi L; Pediatric Nephrology Unit, Regina Margherita Children's Hospital, AOU Città della Salute e della Scienza di Torino, Turin, Italy., Molino D; Pediatric Nephrology and Dialysis Unit, Santobono Children's Hospital, Naples, Italy., Benetti E; Department of Women's and Children's Health, University Hospital of Padua, Padua, Italy., Gianoglio B; Pediatric Nephrology Unit, Regina Margherita Children's Hospital, AOU Città della Salute e della Scienza di Torino, Turin, Italy., Mehmeti F; Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy., Catenacci L; Pediatric Hematology Oncology and Cell Factory, Department of Maternal and Children's Health, Foundation IRCCS Policlinico San Matteo, Pavia, Italy., Rotella J; Pediatric Hematology Oncology and Cell Factory, Department of Maternal and Children's Health, Foundation IRCCS Policlinico San Matteo, Pavia, Italy., Tamburello C; Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy., Moretta A; Pediatric Hematology Oncology and Cell Factory, Department of Maternal and Children's Health, Foundation IRCCS Policlinico San Matteo, Pavia, Italy., Lazzari L; Laboratory of Regenerative Medicine, Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy., Giordano R; Laboratory of Regenerative Medicine, Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy. rosaria.giordano@policlinico.mi.it., Prati D; Laboratory of Regenerative Medicine, Cell Factory, Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy., Montini G; Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via della Commenda 9, 20122, Milan, Italy. giovanni.montini@unimi.it.; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. giovanni.montini@unimi.it.
Jazyk: angličtina
Zdroj: Stem cell research & therapy [Stem Cell Res Ther] 2022 Aug 19; Vol. 13 (1), pp. 420. Date of Electronic Publication: 2022 Aug 19.
DOI: 10.1186/s13287-022-03112-7
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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