title: Neurotrophic factor expression in expandable cell populations from brain samples in living patients with Parkinson's disease.
abstract: Cell-based therapies offer promise for patients with Parkinson's disease (PD); however, durable and effective transplantation substrates need to be defined. This study characterized the feasibility and growth properties of primary cultures established from small-volume brain biopsies taken during deep brain stimulation (DBS) surgery in patients with PD. The lineage and expression of neurotrophic factors with known beneficial actions in PD-affected brain circuitry were also evaluated. Nineteen patients with PD undergoing DBS surgery consented to brain biopsies prior to electrode implantation. Cultures from these samples exhibited exponential and plateau phases of growth and were readily expanded throughout multiple passages. There was robust expression of progenitor markers and the unexpected colocalization of neural and mesenchymal proteins. The oligodendrocyte transcription factor, Olig1, and the myelin-specific sphingolipid, galactocerebroside, were coexpressed with each of glial-derived neurotrophic factor, brain-derived neurotrophic factor, and cerebral dopamine neurotrophic factor. Fluorescence-activated cell sorting demonstrated homogeneous expression of both nestin and Olig1 throughout the expanded cultures. Cells remained viable after a year in cryostorage. These findings confirm the feasibility of small brain biopsies as an expandable source of autologous cell substrate in living patients and demonstrate the complex phenotype of these cells, with implications for therapeutic application in PD and other neurological diseases.
authors.affiliation: 1Department of Clinical Neurological Sciences (Neurosurgery), University of Western Ontario, 339 Windermere Rd., C7-134, London, ON, Canada N6A 5A5. mhebb@uwo.ca.
authors.forename: Hu
authors.initials: H
authors.lastname: Xu
authors.forename: Louiza
authors.initials: L
authors.lastname: Belkacemi
authors.forename: Mandar
authors.initials: M
authors.lastname: Jog
authors.forename: Andrew
authors.initials: A
authors.lastname: Parrent
authors.forename: Matthew O
authors.initials: MO
authors.lastname: Hebb
mesh_terms: D000368:Aged; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: neurodegeneration; transplantation