title: Glial cell line-derived neurotrophic factor-secreting human neural progenitors show long-term survival, maturation into astrocytes, and no tumor formation following transplantation into the spinal cord of immunocompromised rats.
abstract: Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and genetically modified through lentiviral transduction to secrete growth factors shown to have a neurotrophic effect in animal models of neurological disease. hNPCs survive and mature following transplantation into the central nervous system of large and small animals including the rat model of amyotrophic lateral sclerosis. Here we report that hNPCs engineered to express glial cell line-derived neurotrophic factor (GDNF) survive long-term (7.5 months) following transplantation into the spinal cord of athymic nude rats and continue to secrete GDNF. Cell proliferation declined while the number of astrocytes increased, suggesting final maturation of the cells over time in vivo. Together these data show that GDNF-producing hNPCs may be useful as a source of cells for long-term delivery of both astrocytes and GDNF to the damaged central nervous system.
authors.affiliation: Cedars-Sinai Medical Center, Regenerative Medicine Institute, Los Angeles, California, USA.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Gowing
authors.forename: Brandon
authors.initials: B
authors.lastname: Shelley
authors.forename: Kevin
authors.initials: K
authors.lastname: Staggenborg
authors.forename: Amanda
authors.initials: A
authors.lastname: Hurley
authors.forename: Pablo
authors.initials: P
authors.lastname: Avalos
authors.forename: Jesse
authors.initials: J
authors.lastname: Victoroff
authors.forename: Jessica
authors.initials: J
authors.lastname: Latter
authors.forename: Leslie
authors.initials: L
authors.lastname: Garcia
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D053686:Fetal Stem Cells / Q000378:metabolism* / Q000637:transplantation; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D008297:Male; D058953:Neural Stem Cells / Q000378:metabolism* / Q000637:transplantation; D051381:Rats; D011923:Rats, Nude; D013116:Spinal Cord / Q000473:pathology / Q000637:transplantation*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein