Preclinical characterization of DUOC-01, a cell therapy product derived from banked umbilical cord blood for use as an adjuvant to umbilical cord blood transplantation for treatment of inherited metabolic diseases

Cytotherapy
Joanne KurtzbergAndrew E Balber

Abstract

Cord blood (CB) transplantation slows neurodegeneration during certain inherited metabolic diseases. However, the number of donor cells in the brain of patients does not appear to be sufficient to provide benefit until several months after transplant. We developed the cell product DUOC-01 to provide therapeutic effects in the early post-transplant period. DUOC-01 cultures initiated from banked CB units were characterized by use of time-lapse photomicroscopy during the 21-day manufacturing process. Antigen expression was measured by means of flow cytometry and immunocytochemistry; transcripts for cytokines and enzymes by quantitative real-time polymerase chain reaction; activities of lysosomal enzymes by direct biochemical analysis; alloreactivity of DUOC-01 and of peripheral blood (PB) mononuclear cells (MNC) to DUOC-01 by mixed lymphocyte culture methods; and cytokine secretion by Bioplex assays. DUOC-01 cultures contained highly active, attached, motile, slowly proliferating cells that expressed common (cluster of differentiation [CD]11b, CD14 and Iba1), M1 type (CD16, inducible nitric oxide synthase), and M2-type (CD163, CD206) macrophage or microglia markers. Activities of 11 disease-relevant lysosomal enzymes in DUOC-01 pr...Continue Reading

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Citations

Dec 26, 2015·Lancet Neurology·Joshua G HunsbergerP Murali Doraiswamy
Apr 30, 2017·Stem Cells Translational Medicine·Joanne Kurtzberg
Nov 16, 2017·Regenerative Medicine·Pedro S CoutoFrances Verter
Jul 4, 2020·Stem Cells Translational Medicine·Joanne Kurtzberg
May 16, 2019·Bone Marrow Transplantation·Hector MayaniHal E Broxmeyer
Jun 23, 2018·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Heather AlleweltJoanne Kurtzberg
Jun 3, 2021·International Journal of Molecular Sciences·Sarah Cunningham, Holger Hackstein
Jul 10, 2021·Frontiers in Cellular Neuroscience·Georg von JonquieresGary D Housley
Aug 8, 2021·International Journal of Molecular Sciences·Christiane S HampeR Scott McIvor

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