Neurotrophic factor expression in expandable cell populations from brain samples in living patients with Parkinson's disease.
Identifieur interne : 000D21 ( Main/Exploration ); précédent : 000D20; suivant : 000D22Neurotrophic factor expression in expandable cell populations from brain samples in living patients with Parkinson's disease.
Auteurs : Hu Xu [Canada] ; Louiza Belkacemi ; Mandar Jog ; Andrew Parrent ; Matthew O. HebbSource :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ 1530-6860 ] ; 2013.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Brain-Derived Neurotrophic Factor.
- chemical , metabolism : Brain-Derived Neurotrophic Factor.
- metabolism : Neurons, Parkinson Disease.
- physiology : Gene Expression Regulation.
- Aged, Cell Culture Techniques, Humans, Middle Aged.
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.
DOI: 10.1096/fj.12-226555
PubMed: 23825231
Affiliations:
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Hebb</name></author></analytic><series><title level="j">FASEB journal : official publication of the Federation of American Societies for Experimental Biology</title><idno type="eISSN">1530-6860</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Brain-Derived Neurotrophic Factor (genetics)</term><term>Brain-Derived Neurotrophic Factor (metabolism)</term><term>Cell Culture Techniques</term><term>Gene Expression Regulation (physiology)</term><term>Humans</term><term>Middle Aged</term><term>Neurons (metabolism)</term><term>Parkinson Disease (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Brain-Derived Neurotrophic Factor</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Brain-Derived Neurotrophic Factor</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Neurons</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Gene Expression Regulation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Cell Culture Techniques</term><term>Humans</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Belkacemi, Louiza" sort="Belkacemi, Louiza" uniqKey="Belkacemi L" first="Louiza" last="Belkacemi">Louiza Belkacemi</name><name sortKey="Hebb, Matthew O" sort="Hebb, Matthew O" uniqKey="Hebb M" first="Matthew O" last="Hebb">Matthew O. Hebb</name><name sortKey="Jog, Mandar" sort="Jog, Mandar" uniqKey="Jog M" first="Mandar" last="Jog">Mandar Jog</name><name sortKey="Parrent, Andrew" sort="Parrent, Andrew" uniqKey="Parrent A" first="Andrew" last="Parrent">Andrew Parrent</name></noCountry><country name="Canada"><noRegion><name sortKey="Xu, Hu" sort="Xu, Hu" uniqKey="Xu H" first="Hu" last="Xu">Hu Xu</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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