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Gene products promoting remyelination are up-regulated in a cell therapy product manufactured from banked human cord blood.

Publication ,  Journal Article
Scotland, P; Buntz, S; Noeldner, P; Saha, A; Gentry, T; Kurtzberg, J; Balber, AE
Published in: Cytotherapy
June 2017

BACKGROUND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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Published In

Cytotherapy

DOI

EISSN

1477-2566

Publication Date

June 2017

Volume

19

Issue

6

Start / End Page

771 / 782

Location

England

Related Subject Headings

  • Up-Regulation
  • Remyelination
  • Myelin Sheath
  • Monocytes
  • Macrophages
  • Lipopolysaccharide Receptors
  • Immunology
  • Humans
  • Gene Expression Regulation
  • Fetal Blood
 

Citation

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Scotland, P., Buntz, S., Noeldner, P., Saha, A., Gentry, T., Kurtzberg, J., & Balber, A. E. (2017). Gene products promoting remyelination are up-regulated in a cell therapy product manufactured from banked human cord blood. Cytotherapy, 19(6), 771–782. https://doi.org/10.1016/j.jcyt.2017.03.004
Scotland, Paula, Susan Buntz, Pamela Noeldner, Arjun Saha, Tracy Gentry, Joanne Kurtzberg, and Andrew E. Balber. “Gene products promoting remyelination are up-regulated in a cell therapy product manufactured from banked human cord blood.Cytotherapy 19, no. 6 (June 2017): 771–82. https://doi.org/10.1016/j.jcyt.2017.03.004.
Scotland P, Buntz S, Noeldner P, Saha A, Gentry T, Kurtzberg J, et al. Gene products promoting remyelination are up-regulated in a cell therapy product manufactured from banked human cord blood. Cytotherapy. 2017 Jun;19(6):771–82.
Scotland, Paula, et al. “Gene products promoting remyelination are up-regulated in a cell therapy product manufactured from banked human cord blood.Cytotherapy, vol. 19, no. 6, June 2017, pp. 771–82. Pubmed, doi:10.1016/j.jcyt.2017.03.004.
Scotland P, Buntz S, Noeldner P, Saha A, Gentry T, Kurtzberg J, Balber AE. Gene products promoting remyelination are up-regulated in a cell therapy product manufactured from banked human cord blood. Cytotherapy. 2017 Jun;19(6):771–782.
Journal cover image

Published In

Cytotherapy

DOI

EISSN

1477-2566

Publication Date

June 2017

Volume

19

Issue

6

Start / End Page

771 / 782

Location

England

Related Subject Headings

  • Up-Regulation
  • Remyelination
  • Myelin Sheath
  • Monocytes
  • Macrophages
  • Lipopolysaccharide Receptors
  • Immunology
  • Humans
  • Gene Expression Regulation
  • Fetal Blood