title: Liver growth factor promotes the survival of grafted neural stem cells in a rat model of Parkinson's disease.
abstract: Neural stem cells (NSCs) with self-renewal and multilineage potential are considered good candidates for cell replacement of damaged nerve tissue. Several studies have focused on the ability of the neurotrophic factors coadministration to improve the efficiency of grafted NSCs. Liver growth factor (LGF) is an hepatic mitogen that promotes regeneration of damaged tissues, including brain tissue. It has neurogenic activity and has partially restored the nigrostriatal dopaminergic system in an experimental model of Parkinson's disease. Present results demonstrate that in the dopamine- depleted striatum of 6-hydroxydopamine-lesioned rats, grafted NSCs retained their ability to differentiate into neurons, astrocytes, and oligodendrocytes. NSCs also differentiated into microglia/macrophages and endothelial cells. Thus, 23 ± 5.6% of them were inmunoreactive for isolectin IB4, and a small population integrated into blood vessels, showing an endothelial-like morphology. Intrastriatal infusion of LGF promoted the viability of the implants, and favored their differentiation to an endothelial-like phenotype. Moreover, LGF infusion raised the expression of the anti-apoptotic protein Bcl-2 by 3.9 ± 0.9 fold without affecting the levels of the pro-apoptotic protein Bax. Since LGF-treated rats also showed a significant reduction in apomorphine-induced rotational behavior, our results suggest that administration of this factor might be a convenient treatment for Parkinson's disease cell replacement therapies based on NSCs transplantation.
authors.affiliation: Servicio de Neurobiologia, Hospital Ramon y Cajal, Madrid, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Reimers
authors.forename: Cristina
authors.initials: C
authors.lastname: Osuna
authors.forename: Rafael
authors.initials: R
authors.lastname: Gonzalo-Gobernado
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Herranz
authors.forename: Juan Jose
authors.initials: JJ
authors.lastname: Diaz-Gil
authors.forename: Adriano
authors.initials: A
authors.lastname: Jimenez-Escrig
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Asensio
authors.forename: Cristina
authors.initials: C
authors.lastname: Miranda
authors.forename: Macarena
authors.initials: M
authors.lastname: Rodriguez-Serrano
authors.forename: Eulalia
authors.initials: E
authors.lastname: Bazan
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016627:Oxidopamine / Q000008:administration & dosage; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012709:Serum Albumin / Q000008:administration & dosage*; D000075462:Serum Albumin, Human; D033581:Stem Cell Transplantation
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012709:Serum Albumin; C053498:albumin-bilirubin complex; D016627:Oxidopamine; D001663:Bilirubin; D000075462:Serum Albumin, Human