title: Transplantation of fetal ventral mesencephalic progenitor cells overexpressing high molecular weight fibroblast growth factor 2 isoforms in 6-hydroxydopamine lesioned rats.
abstract: Fibroblast growth factor-2 (FGF-2) is a potent neurotrophic factor promoting survival of dopaminergic (DA) neurons in vitro and in vivo. FGF-2 is expressed in different isoforms representing distinct translation products from a single mRNA. For this study, we focused on the high molecular weight (HMW) isoform, which, after non-viral plasmid-based overexpression in embryonic day 12 (E12) rat ventral mesencephalon (VM)-derived cells, revealed increased numbers of tyrosine hydroxylase-positive (TH(+)) cells in a 'colayer' cell culture model. To determine the therapeutic potential of VM cells producing FGF-2-HMW as their 'own' neurotrophic factor, we transplanted cell suspensions obtained from such in vitro modified and differentiated cell cultures into the 6-hydroxydopamine (6-OHDA) hemiparkinsonian rat model. Animals, having received either non-transfected cells, empty-control transfected, or FGF-2-HMW-plasmid transfected cells, were analyzed in two different transplantation paradigms each using 172,000 or 520,000 cells, respectively. The behavioral performances in the amphetamine- and apomorphine-induced rotational test as well as in the cylinder test were evaluated for up to thirteen weeks post transplantation (postTX). Finally, the integration of the grafted cells into the host striatum was analyzed by immunohistochemical measurements. Those analyses revealed improvements of behavioral deficits in all five groups receiving DA neuron grafts, except for amphetamine-induced rotation of the FGF-2-HMW small graft group. Altogether, genetic modification with the FGF-2-HMW-plasmid did not further improve functional recovery compared to the control groups and had no influence on either the number of surviving DA neurons or on the density of outgrowing TH(+) fibers.
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Rumpel
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hohmann
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Klein
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wesemann
authors.affiliation: Centre for Systems Neuroscience (ZSN), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany; Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Baumgärtner
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ratzka
authors.affiliation: Institute of Neuroanatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany; Centre for Systems Neuroscience (ZSN), Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: grothe.claudia@mh-hannover.de.
authors.forename: C
authors.initials: C
authors.lastname: Grothe
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000166:cytology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D008636:Mesencephalon / Q000166:cytology*; D009043:Motor Activity; D016627:Oxidopamine; D010300:Parkinson Disease / Q000628:therapy*; D020033:Protein Isoforms; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase
chemical_list: D020033:Protein Isoforms; D016222:Fibroblast Growth Factor 2; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: Parkinson’s disease; brain repair; dopaminergic neuron; neurotrophic factor; nucleofection; striatum