title: Gene products promoting remyelination are up-regulated in a cell therapy product manufactured from banked human cord blood.
abstract: DUOC-01, a cell product being developed to treat demyelinating conditions, is composed of macrophages that arise from CD14+monocytes in the mononuclear cell (MNC) population of banked cord blood (CB). This article demonstrates that expression of multiple gene products that promote remyelination is rapidly up-regulated during manufacturing of DUOC-01 from either MNC or purified CB CD14+monocytes.
  
  
  
  Cell cultures were initiated with MNC or with immunoselected CD14+monocytes isolated from the same CB unit. Cell products present in these cultures after 2 and 3 weeks were compared by three methods. First, quantitative polymerase chain reaction was used to compare expression of 77 transcripts previously shown to be differentially expressed by freshly isolated, uncultured CB CD14+monocytes and DUOC-01. Second, accumulation of 16 soluble proteins in the culture medium was measured by Bioplex methods. Third, whole transcriptomes of the cell products were compared by microarray analysis.
  
  
  
  Key transcripts in multiple pathways that promote remyelination were up-regulated in DUOC-01, and substantial secretion of proteins corresponding to many of these transcripts was detected. Cell products manufactured from MNC or from CD14+monocytes were similar with regard to all metrics. Upregulation of gene products characteristic of DUOC-01 was largely completed within 14 days of culture.
  
  
  
  We demonstrate that expression of multiple gene products that promote remyelination is up-regulated during the first 2 weeks of manufacturing of DUOC-01. Measuring these mechanistically important transcripts and proteins will be useful in monitoring manufacturing, evaluating manufacturing changes, and developing mechanism-based product potency assays.
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: 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: 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: 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: 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: 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. Electronic address: andrew.balber@duke.edu.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Balber
mesh_terms: D001771:Blood Banks; D002478:Cells, Cultured; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism; D000074586:Remyelination; D015854:Up-Regulation
chemical_list: D018950:Lipopolysaccharide Receptors
keywords: cord blood; macrophage; monocytes; remyelination