A cord blood monocyte-derived cell therapy product accelerates brain remyelination
| Autor: | Pamela K. Noeldner, Susan Buntz, Paula Scotland, Arjun Saha, Joanne Kurtzberg, Sachit Patel, Amy Wollish, Glenn K. Matsushima, Li Xu, Tracy Gentry, Andrew E. Balber, Jesse D. Troy, Aruni Gunaratne |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male CD14 Cell- and Tissue-Based Therapy Lipopolysaccharide Receptors Mice SCID Biology Peripheral blood mononuclear cell Monocytes Cell therapy 03 medical and health sciences Mice 0302 clinical medicine Mice Inbred NOD medicine Animals Humans Remyelination Microglia Brain General Medicine Fetal Blood Oligodendrocyte 3. Good health Cell biology Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Gliosis Cord blood Immunology medicine.symptom 030217 neurology & neurosurgery Research Article |
| Zdroj: | JCI insight. 1(13) |
| ISSN: | 2379-3708 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|