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A cord blood monocyte-derived cell therapy product accelerates brain remyelination.

Publication ,  Journal Article
Saha, A; Buntz, S; Scotland, P; Xu, L; Noeldner, P; Patel, S; Wollish, A; Gunaratne, A; Gentry, T; Troy, J; Matsushima, GK; Kurtzberg, J; Balber, AE
Published in: JCI Insight
August 18, 2016

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/IL2Rγnull mice 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.

Duke Scholars

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Published In

JCI Insight

DOI

ISSN

2379-3708

Publication Date

August 18, 2016

Volume

1

Issue

13

Start / End Page

e86667

Location

United States

Related Subject Headings

  • Remyelination
  • Monocytes
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipopolysaccharide Receptors
  • Humans
  • Fetal Blood
 

Citation

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Saha, A., Buntz, S., Scotland, P., Xu, L., Noeldner, P., Patel, S., … Balber, A. E. (2016). A cord blood monocyte-derived cell therapy product accelerates brain remyelination. JCI Insight, 1(13), e86667. https://doi.org/10.1172/jci.insight.86667
Saha, Arjun, Susan Buntz, Paula Scotland, Li Xu, Pamela Noeldner, Sachit Patel, Amy Wollish, et al. “A cord blood monocyte-derived cell therapy product accelerates brain remyelination.JCI Insight 1, no. 13 (August 18, 2016): e86667. https://doi.org/10.1172/jci.insight.86667.
Saha A, Buntz S, Scotland P, Xu L, Noeldner P, Patel S, et al. A cord blood monocyte-derived cell therapy product accelerates brain remyelination. JCI Insight. 2016 Aug 18;1(13):e86667.
Saha, Arjun, et al. “A cord blood monocyte-derived cell therapy product accelerates brain remyelination.JCI Insight, vol. 1, no. 13, Aug. 2016, p. e86667. Pubmed, doi:10.1172/jci.insight.86667.
Saha A, Buntz S, Scotland P, Xu L, Noeldner P, Patel S, Wollish A, Gunaratne A, Gentry T, Troy J, Matsushima GK, Kurtzberg J, Balber AE. A cord blood monocyte-derived cell therapy product accelerates brain remyelination. JCI Insight. 2016 Aug 18;1(13):e86667.

Published In

JCI Insight

DOI

ISSN

2379-3708

Publication Date

August 18, 2016

Volume

1

Issue

13

Start / End Page

e86667

Location

United States

Related Subject Headings

  • Remyelination
  • Monocytes
  • Mice, SCID
  • Mice, Inbred NOD
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Lipopolysaccharide Receptors
  • Humans
  • Fetal Blood