Cell replacement therapies to promote remyelination in a viral model of demyelination.
Persistent infection of the central nervous system (CNS) of mice with the neuroadapted JHM strain of mouse hepatitis (MHV) is characterized by ongoing demyelination mediated by inflammatory T cells and macrophages that is similar both clinically and histologically with the human demyelinating disease multiple sclerosis (MS). Although extensive demyelination occurs in mice persistently infected with MHV there is only limited remyelination. Therefore, the MHV model of demyelination is a relevant model for studying disease and evaluating therapeutic approaches to protect cells of the oligodendrocyte lineage and promote remyelination. This concept is further highlighted as the etiology of MS remains enigmatic, but viruses have long been considered as potential triggering agents in initiating and/or maintaining MS symptoms. As such, understanding mechanisms associated with promoting repair within the CNS in the context of a persistent viral infection is critical given the possible viral etiology of MS. This review focuses on recent studies using either mouse neural stem cells (NSCs) or human oligodendrocyte progenitor cells (OPCs) derived from human embryonic stem cell (hESC) to promote remyelination in mice persistently infected with MHV. In addition, the potential role for chemokines in positional migration of transplanted cells is addressed.
Tirotta
Emanuele
E
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine, CA 92697, USA.
Carbajal
Kevin S
KS
Schaumburg
Chris S
CS
Whitman
Lucia
L
Lane
Thomas E
TE
D000818:Animals; D019070:Cell Lineage / Q000276:immunology; D018352:Coronavirus Infections / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003711:Demyelinating Diseases / Q000473:pathology / Q000628:therapy* / Q000821:virology*; D004195:Disease Models, Animal; D018792:Encephalitis, Viral / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D006517:Murine hepatitis virus / Q000276:immunology*; D009413:Nerve Fibers, Myelinated / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000276:immunology*; D033581:Stem Cell Transplantation / Q000379:methods* / Q000639:trends