First clinical application of cord blood mesenchymal stromal cells in children with multi-drug resistant nephrotic syndrome.
Advanced therapy medical products
Children
Cord-blood-derived mesenchymal stromal cells
Idiopathic nephrotic syndrome
Mesenchymal stromal cells
Multi-drug resistant nephrotic syndrome
Journal
Stem cell research & therapy
ISSN: 1757-6512
Titre abrégé: Stem Cell Res Ther
Pays: England
ID NLM: 101527581
Informations de publication
Date de publication:
19 08 2022
19 08 2022
Historique:
received:
23
04
2022
accepted:
03
08
2022
entrez:
19
8
2022
pubmed:
20
8
2022
medline:
24
8
2022
Statut:
epublish
Résumé
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. 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 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. 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.
Sections du résumé
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
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.
Identifiants
pubmed: 35986374
doi: 10.1186/s13287-022-03112-7
pii: 10.1186/s13287-022-03112-7
pmc: PMC9389735
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
420Informations de copyright
© 2022. The Author(s).
Références
J Clin Epidemiol. 2015 Nov;68(11):1375-9
pubmed: 26146089
Cell Death Dis. 2016 Jan 21;7:e2062
pubmed: 26794657
Lancet. 2018 Jul 7;392(10141):61-74
pubmed: 29910038
N Engl J Med. 2014 Mar 27;370(13):1268-70
pubmed: 24670185
Stem Cells Int. 2018 Sep 4;2018:3038565
pubmed: 30254681
Cytotherapy. 2006;8(4):315-7
pubmed: 16923606
Stem Cell Res Ther. 2019 Jun 21;10(1):182
pubmed: 31227011
Transplantation. 2007 Jan 15;83(1):71-6
pubmed: 17220794
Ann Hematol. 2018 Oct;97(10):1941-1950
pubmed: 29947972
J Am Soc Nephrol. 2009 Mar;20(3):629-37
pubmed: 19158356
J Am Soc Nephrol. 2018 Feb;29(2):362-375
pubmed: 29191959
Cell Death Differ. 2018 Jul;25(7):1209-1223
pubmed: 29238069
Mediators Inflamm. 2013;2013:434010
pubmed: 23533306
J Am Soc Nephrol. 2009 Jan;20(1):57-67
pubmed: 19020006
Transfusion. 2014 May;54(5):1418-37
pubmed: 24898458
Ital J Pediatr. 2017 Apr 21;43(1):41
pubmed: 28427453
Transplantation. 2010 Dec 27;90(12):1312-20
pubmed: 21042238
Front Immunol. 2020 Jun 09;11:1156
pubmed: 32582218
Annu Rev Pathol. 2011;6:457-78
pubmed: 21073342
Blood. 2007 Nov 15;110(10):3499-506
pubmed: 17664353
Cytotherapy. 2005;7(5):393-5
pubmed: 16236628
Pediatr Nephrol. 2013 Feb;28(2):257-64
pubmed: 23052656
Exp Hematol. 2009 Dec;37(12):1445-53
pubmed: 19772890
Pediatr Nephrol. 2017 May;32(5):835-841
pubmed: 28213687
Drug Des Devel Ther. 2015 Aug 20;9:4825-34
pubmed: 26316716
Blood. 2002 May 15;99(10):3838-43
pubmed: 11986244
Sci Rep. 2021 Mar 24;11(1):6751
pubmed: 33762629
Biol Blood Marrow Transplant. 2018 Nov;24(11):2365-2370
pubmed: 30031938
Nat Rev Nephrol. 2018 Aug;14(8):493-507
pubmed: 29895977
Blood. 2005 Feb 15;105(4):1815-22
pubmed: 15494428
Pediatr Nephrol. 2008 Mar;23(3):481-5
pubmed: 17973121
Regen Med. 2017 Oct;12(7):803-813
pubmed: 29115906
Stem Cell Res Ther. 2020 Feb 28;11(1):91
pubmed: 32111238
Haematologica. 2007 Jul;92(7):881-8
pubmed: 17606437
Cell Immunol. 2018 Apr;326:86-93
pubmed: 29221689
Sci Transl Med. 2017 Nov 15;9(416):
pubmed: 29141887
J Nephrol. 2020 Aug;33(4):849-857
pubmed: 31617157
J Am Soc Nephrol. 2012 Jun;23(6):1117-24
pubmed: 22581994
Stem Cells Dev. 2015 Jan 1;24(1):104-14
pubmed: 25046283
N Engl J Med. 2007 Jun 28;356(26):2751-2
pubmed: 17596616
Pediatr Nephrol. 2009 Sep;24(9):1683-90
pubmed: 19499249