Uniform TitleTherapeutic potential of radial glial RG3.6 cells in rat spinal cord injury
NameChang, Yu-Wen (author), Grumet, Martin (chair), Firestein, Bonnie (internal member), Nowakowski, Richard (internal member), Young, Wise (internal member), Ratan, Rajiv (outside member), Rutgers University, Graduate School - New Brunswick,
Spinal cord--Wounds and injuries,
DescriptionSpinal cord injury (SCI) triggers a cascade of pathophysiological changes that lead to secondary tissue damage after the mechanical insult. Early after SCI, cells are disrupted and excitotoxic amino acids (e.g. glutamate) are released. Inflammatory cytokines and chemokines are quickly induced upon injury, followed by leukocyte infiltration (e.g. neutrophil and macrophage). Neurons and glia undergo massive necrotic cell death and apoptosis. Axons become progressively degenerated and extracellular substrate deposits in the lesion site, which leads to cyst and scar formation.
Cell-based therapies have been widely applied during SCI sub-acute phase and at least one mechanism associated with behavioral improvement is promotion of axonal remyelination and regeneration. However, the efficacy of cell transplantation at acute SCI and associated mechanism has rarely been studied.
Radial glial cells are essential in guiding and supporting neuronal migration during central nervous system development. They are neural stem cells and have trophic functions under certain conditions. In this thesis, our goal is to understand whether acute transplantation of radial glia can mitigate deleterious responses in the injured spinal cord tissue and promote functional recovery. RG3.6 is a stable neural stem cell clone derived from E13.5 cortex and has radial glial phenotypes including bipolar shape, expression of BLBP and GLAST, and support of neurite growth. Transplanted in normal spinal cord, RG3.6 retained radial glial phenotype and actively migrated along rostral-caudal axis of spinal cord and integrated nicely with host tissue. In SCI, acute transplantation of RG3.6 significantly improved locomotion recovery as early as 2 days post injury. The functional recovery may be associated with fewer infiltrating macrophages, less CSPG deposition, and more axonal preservation. At the molecular level, RG3.6 cell enhanced the expression of genes that are involved in tissue defense and stem cell development.
In summary, radial glia in acute SCI modulated host responses to the injury by mediating certain gene expressions at early times, suppressed neuroinflammation, and supported and reorganized axons during later phases. Our results provide different perspectives of cell-based therapy for acute SCI.
NoteIncludes bibliographical references (p. 117-137).
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.