title: A cord blood monocyte-derived cell therapy product accelerates brain remyelination.
abstract: Microglia and monocytes play important roles in regulating brain remyelination. We developed DUOC-01, a cell therapy product intended for treatment of demyelinating diseases, from banked human umbilical cord blood (CB) mononuclear cells. Immunodepletion and selection studies demonstrated that DUOC-01 cells are derived from CB CD14+monocytes. We compared the ability of freshly isolated CB CD14+monocytes and DUOC-01 cells to accelerate remyelination of the brains of NOD/SCID/IL2Rγnullmice following cuprizone feeding-mediated demyelination. The corpus callosum of mice intracranially injected with DUOC-01 showed enhanced myelination, a higher proportion of fully myelinated axons, decreased gliosis and cellular infiltration, and more proliferating oligodendrocyte lineage cells than those of mice receiving excipient. Uncultured CB CD14+monocytes also accelerated remyelination, but to a significantly lesser extent than DUOC-01 cells. Microarray analysis, quantitative PCR studies, Western blotting, and flow cytometry demonstrated that expression of factors that promote remyelination including PDGF-AA, stem cell factor, IGF1, MMP9, MMP12, and triggering receptor expressed on myeloid cells 2 were upregulated in DUOC-01 compared to CB CD14+monocytes. Collectively, our results show that DUOC-01 accelerates brain remyelination by multiple mechanisms and could be beneficial in treating demyelinating conditions.
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Arjun
authors.initials: A
authors.lastname: Saha
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Buntz
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Scotland
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Noeldner
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Sachit
authors.initials: S
authors.lastname: Patel
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Wollish
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Aruni
authors.initials: A
authors.lastname: Gunaratne
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Gentry
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Troy
authors.affiliation: Department of Microbiology and Immunology, UNC Neuroscience Center, Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Glenn K
authors.initials: GK
authors.lastname: Matsushima
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.affiliation: Robertson Clinical and Translational Cell Therapy Program, Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Balber
mesh_terms: D000818:Animals; D001921:Brain; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D018950:Lipopolysaccharide Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009000:Monocytes / Q000166:cytology*; D000074586:Remyelination
chemical_list: D018950:Lipopolysaccharide Receptors