Cell therapy successfully promotes axon remyelination in an animal model.

ft Cell therapy promotes axon remyelination in a mouse model - neuroinnovations

Demyelinating diseases, such as multiple sclerosis and leukodystrophy, are characterized by damage to the protective myelin sheath that surrounds the axons of neurons. This demyelination can be caused by an autoimmune response or impaired myelin production by oligodendrocytes. Now, a study from Duke University shows that a cell therapy product called DUOC-01 can accelerate remyelination of axons in mice treated with a demyelinating chemical agent.  The team state that their results suggest a cord blood-derived cell product can promote neuronal repair and remyelination, meaning it could be possible that the DUOC-01 cell therapy could benefit patients with demyelinating diseases.  The opensource study is published in the journal JCI Insight.

Previous studies have shown that microglia play critical but incompletely understood roles in propagation and resolution of central nervous system injuries. These cells modulate neuroinflammation, produce factors that regulate activities of astrocytes, oligodendrocytes, and neurons, and clear debris to provide an environment for oligodendrocytes to begin to remyelinate neurons.  Bone marrow–derived, circulating blood monocytes constitute another potential source of infiltrating phagocytic cells that can cause CNS damage, however, limited information is available concerning the role of human blood monocytes in the dynamics of repair of brain injury.  The current study shows DUOC-01 cells, which are derived from banked umbilical cord blood, accelerates brain remyelination by multiple mechanisms and could be beneficial in treating demyelinating conditions.

The current study assessed the ability of DUOC-01 to promote remyelination of mouse brain after cuprizone-induced (CPZ-induced) demyelination.  DUOC-01 cells were transplanted into mice following toxic demyelination.  Results show that DUOC-01 treatment resulted in faster remyelination and promoted the differentiation of oligodendrocyte progenitor cells.

Data findings show that the DUOC-01 cell product accelerates brain remyelination following CPZ feeding.  The lab state that they also show that CD14+ monocytes that give rise to DUOC-01 also accelerate remyelination, although significantly less actively than DUOC-01 cells. Results via a comparison of whole-genome expression arrays of CD14+ monocytes and DUOC-01 revealed large differences in gene expression, and helped identify candidate molecules that may participate in remyelination.

The team surmise that their findings show DUOC-01 accelerates brain remyelination by multiple mechanisms and could be beneficial in treating demyelinating conditions.  For the future, the researchers state that the biological activity of DUOC-01 reported suggests that it has potential for the treatment of disorders of myelination in the clinic and that these preclinical studies should be considered as part of the clinical development program of this potentially novel cord blood-derived cell therapy product.

Source: Duke University School of Medicine

 

LFB-PAS staining analysis of effect of DUOC-01 treatment on remyelination following cessation of cuprizone (CPZ) treatment.  LFB-PAS staining 1 week after intracranial injection of CD14+ monocytes (lower panels), and DUOC-1 cells (middle panels), in CPZ-fed NSG mice. Midline corpus callosum (CC) area is shown by dotted green line. Scale bars: 2,000 μm (×20 magnification) and 100 μm (×400 magnification).  A cord blood monocyte–derived cell therapy product accelerates brain remyelination.  Balber et al 2016.

LFB-PAS staining analysis of effect of DUOC-01 treatment on remyelination following cessation of cuprizone (CPZ) treatment. LFB-PAS staining 1 week after intracranial injection of CD14+ monocytes (lower panels), and DUOC-1 cells (middle panels), in CPZ-fed NSG mice. Midline corpus callosum (CC) area is shown by dotted green line. Scale bars: 2,000 μm (×20 magnification) and 100 μm (×400 magnification). A cord blood monocyte–derived cell therapy product accelerates brain remyelination. Balber et al 2016.

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