Duoc-01, a Cord Blood Derived Cell Therapy Product, Ameliorates Experimental Autoimmune Encephalomyelitis

Abstract

DUOC-01 is a cord-blood derived, macrophage-based cell therapy product, developed by our group to treat demyelinating conditions of the central nervous system. Recently, we demonstrated that DUOC-01 accelerated remyelination, decreased gliosis, and reduced cellular infiltration in the corpus callosum of immune-incompetent mice treated with cuprizone. To explore the mechanism and investigate whether DUOC-01 will be effective in other experimental models of demyelination, we tested DUOC-01 in lysophosphatidylcholine (LPC) mediated demyelinated murine organotypic cerebellar brain slices and a mouse model of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. In the cerebellar brain slices, we found that DUOC-01 enhanced remyelination, reduced gliosis, and promoted the proliferation of oligodendrocyte progenitor cells in brain slices demyelinated by LPC compared to the untreated control samples. When we injected DUOC-01 cells into the cerebrospinal fluid of mice immunized for EAE, we found decreased severity of clinical disease compared to the vehicle injected control. Currently we are analyzing single cell sequencing data to determine various populations present in DUOC-01 cultures and to understand the functional pathways responsible for promoting remyelination and reducing neuroinflammation. Overall, our data suggest that DUOC-01 could be beneficial in treating diverse neurological conditions with demyelination.