Transplantation of iPSC-derived neural progenitor cells promotes clinical recovery and repair in response to murine coronavirus-induced neurologic disease

Intracranial inoculation of susceptible strains of mice with the neuroadapted JHM strain of mouse hepatitis virus (JHMV, a member of the Coronaviridae family of viruses) results in an acute encephalomyelitis characterized by widespread growth of virus in astrocytes, microglia, and oligodendrocytes with relative sparing of neurons. Virus-specific CD4+ and CD8+ T cells infiltrate into the central nervous system in response to infection and control viral replication through secretion of interferon gamma as well as cytolytic activity. Nonetheless, virus persists in white matter tracts, and animals develop an immune-mediated demyelinating disease in which both T cells and macrophages amplify white matter damage. For the past decade, we have explored the therapeutic potential of human neural progenitor cells derived from pluripotent stem cells in promoting clinical recovery associated with remyelination of demyelinated axons following intraspinal transplantation. This chapter highlights recent studies from our laboratories demonstrating that tissue repair is associated with the emergence of regulatory T cells in response to transplantation of NPCs.