DUOC-01, a cord blood derived cell therapy product, ameliorates experimental autoimmune encephalomyelitis, a murine model for multiple sclerosis

Abstract

Background & Aim We have developed an umbilical cord-blood derived, macrophage-like cell therapy, DUOC-01, to treat demyelinating conditions of the central nervous system. Previously, we showed that DUOC-01 accelerated remyelination, decreased gliosis, and reduced cellular infiltration in the brain of immune-incompetent mice exposed to the demyelinating agent, cuprizone. To further explore the mechanism of action and investigate whether DUOC-01 will be effective in other experimental models of demyelination, we tested DUOC-01 in the experimental autoimmune encephalomyelitis (EAE) model, an animal model used to study multiple sclerosis (MS). Methods, Results & Conclusion EAE was induced in C57BL/6 mice by immunizing with myelin oligodendrocyte glycoprotein peptide (MOG35-55) in complete Freund's adjuvant. We have previously established in a phase I trial of intrathecally administered DUOC-01 cells in patients with leukodystrophies, that DUOC-01 is formulated in hydrocortisone (HC) for infusion in the clinic. Therefore, to mimic the practice in the clinic, DUOC-01 cells were incubated in Ringer's Lactate with 3mg/mL HC at a dilution of 1 × 106 cells/ml for 2 hours at room temperature prior to injection. DUOC-01 cells were then administered at a dose of 3 × 105cells/mouse into the cerebrospinal fluid by a single intra-cisterna magna injection at the point when mice started showing early disease symptoms of EAE. Clinical score was recorded for next several days. Compared to mice injected with Ringer's (n=9), mice injected with DUOC-01 (n=9) had decreased severity of the disease, as indicated by lower clinical scores based on severity of ascending paralysis. The spinal cords of mice in the cohorts were studied histopathologically and those with mice injected with DUOC-01 had reduced inflammation and lower cellular infiltration compared to spinal cords of mice injected with Ringer's. The overall number of CD45+ immune cells were less in spinal cords of mice treated with DUOC-01 cells compared to the Ringer's injected mice. Most strikingly, among the various cell types, the number of neutrophils present in the spinal cords from the DUOC-01 treated group was less than the Ringer's treated samples. Presently we are exploring the mechanism(s) through which DUOC-01 cells promote remyelination and decrease immune cell infiltration. In brief, our data suggest that DUOC-01 cell therapy product could be beneficial in treating MS and other diverse neurological conditions with demyelination.