title: Multifaceted roles of BDNF and FGF2 in human striatal primordium development. An in vitro study.
abstract: Grafting fetal striatal cells into the brain of Huntington's disease (HD) patients has raised certain expectations in the past decade as an effective cell-based-therapy for this devastating condition. We argue that the first requirement for successful transplantation is defining the window of plasticity for the striatum during development when the progenitor cells, isolated from their environment, are able to maintain regional-specific-identity and to respond appropriately to cues. The primary cell culture from human fetal striatal primordium described here consists of a mixed population of neural stem cells, neuronal-restricted progenitors and striatal neurons. These cells express trophic factors, such as BDNF and FGF2. We show that these neurotrophins maintain cell plasticity, inducing the expression of neuronal precursor markers and cell adhesion molecules, as well as promoting neurogenesis, migration and survival. We propose that BDNF and FGF2 play an important autocrine-paracrine role during early striatum development in vivo and that their release by fetal striatal grafts may be relevant in the setting of HD cell therapy.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Sarchielli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Mirca
authors.initials: M
authors.lastname: Marini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Ambrosini
authors.affiliation: Department of Experimental and Clinical Biomedical Science "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Mazzanti
authors.affiliation: Department of Experimental and Clinical Biomedical Science "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Pinzani
authors.affiliation: Department of Experimental and Clinical Biomedical Science "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Barletta
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Ballerini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Paternostro
authors.affiliation: Department of Neuroscience and NEUROFARBA, University of Florence, Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Paganini
authors.affiliation: Department of Experimental and Clinical Biomedical Science "Mario Serio", University of Florence, Florence, Italy.
authors.forename: Berardino
authors.initials: B
authors.lastname: Porfirio
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Morelli
authors.affiliation: Department of Surgery and Translational Medicine, University of Florence, Florence, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Gallina
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
authors.forename: Gabriella B
authors.initials: GB
authors.lastname: Vannelli
mesh_terms: D000941:Antigens / Q000235:genetics / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D005333:Fetus; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D019081:O Antigens / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D015703:Antigens, CD; D019208:Brain-Derived Neurotrophic Factor; D015815:Cell Adhesion Molecules; D016222:Fibroblast Growth Factor 2; D009419:Nerve Tissue Proteins; D019081:O Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4
keywords: Fetal graft; Huntington's disease; Neurotrophins; Seladin-1; Striatal neuroblasts