title: Transplantation of undifferentiated human mesenchymal stem cells protects against 6-hydroxydopamine neurotoxicity in the rat.
abstract: Stem cells have been increasingly recognized as a potential tool to replace or support cells damaged by the neurodegenerative process that underlies Parkinson's disease (PD). In this frame, human adult mesenchymal stem cells (hMSCs) have been proposed as an attractive alternative to heterologous embryonic or neural precursor cells. To address this issue, in this study we implanted undifferentiated hMSCs into the striatum of rats bearing a lesion of the nigrostriatal pathway induced by local injection of 6-hydroxydopamine (6-OHDA), a widely recognized rodent model of PD. Before grafting, cultured hMSCs expressed markers of both undifferentiated and committed neural cells, including nestin, GAP-43, NSE, beta-tubulin III, and MAP-2, as well as several cytokine mRNAs. No glial or specific neuronal markers were detected. Following transplantation, some hMSCs acquired a glial-like phenotype, as shown by immunoreactivity for glial fibrillary acid protein (GFAP), but only in animals bearing the nigrostriatal lesion. More importantly, rats that received the striatal graft showed increased survival of both cell bodies and terminals of dopaminergic, nigrostriatal neurons, coupled with a reduction of the behavioral abnormalities (apomorphine-induced turning behavior) associated with the lesion. No differentiation of the MSCs toward a neuronal (dopaminergic) phenotype was observed in vivo. In conclusion, our results suggest that grafted hMSCs exert neuroprotective effects against nigrostriatal degeneration induced by 6-OHDA. The mechanisms underlying this effect remain to be clarified, although it is likely that the acquisition of a glial phenotype by grafted hMSCs may lead to the release of prosurvival cytokines within the lesioned striatum.
authors.affiliation: Interdepartmental Research Center for Parkinson's Disease, IRCCS Neurological Institute "C. Mondino," Pavia, Italy. fabio.blandini@mondino.it <fabio.blandini@mondino.it>
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
authors.forename: Lidia
authors.initials: L
authors.lastname: Cova
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Armentero
authors.forename: Eleonora
authors.initials: E
authors.lastname: Zennaro
authors.forename: Giovanna
authors.initials: G
authors.lastname: Levandis
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bossolasco
authors.forename: Cinzia
authors.initials: C
authors.lastname: Calzarossa
authors.forename: Manuela
authors.initials: M
authors.lastname: Mellone
authors.forename: Busca
authors.initials: B
authors.lastname: Giuseppe
authors.forename: Giorgio Lambertenghi
authors.initials: GL
authors.lastname: Deliliers
authors.forename: Elio
authors.initials: E
authors.lastname: Polli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nappi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology
chemical_list: D015415:Biomarkers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D016627:Oxidopamine