title: Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells.
abstract: Parkinson's disease is a common neurodegenerative disorder, which is due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and for which no definitive cure is currently available. Cellular functions in mouse and human tissues can be restored after fusion of bone marrow (BM)-derived cells with a variety of somatic cells. Here, after transplantation of hematopoietic stem and progenitor cells (HSPCs) in the SNpc of two different mouse models of Parkinson's disease, we significantly ameliorated the dopaminergic neuron loss and function. We show fusion of transplanted HSPCs with neurons and with glial cells in the ventral midbrain of Parkinson's disease mice. Interestingly, the hybrids can undergo reprogramming in vivo and survived up to 4weeks after transplantation, while acquiring features of mature astroglia. These newly generated astroglia produced Wnt1 and were essential for functional rescue of the dopaminergic neurons. Our data suggest that glial-derived hybrids produced upon fusion of transplanted HSPCs in the SNpc can rescue the Parkinson's disease phenotype via a niche-mediated effect, and can be exploited as an efficient cell-therapy approach.
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Wassim
authors.initials: W
authors.lastname: Altarche-Xifro
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Umberto
authors.initials: U
authors.lastname: di Vicino
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Muñoz-Martin
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain; Department of Neurochemistry and Neuropharmacology, IIBB-CSIC (Consejo Superior de Investigaciones Científicas), Barcelona, Spain.
authors.forename: Analía
authors.initials: A
authors.lastname: Bortolozzi
authors.affiliation: Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute and Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Bové
authors.affiliation: Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute and Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, Spain; Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona (UAB), Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Vila
authors.affiliation: Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain. Electronic address: pia.cosma@crg.es.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Cosma
mesh_terms: D000818:Animals; D002452:Cell Count; D002459:Cell Fusion; D002470:Cell Survival; D065150:Cellular Reprogramming; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism* / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006822:Hybrid Cells; D008297:Male; D051379:Mice; D009457:Neuroglia / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology; D060449:Wnt Signaling Pathway
chemical_list: D004298:Dopamine
keywords: Astroglia; Cell fusion; Hematopoietic stem and progenitor cells; Intracerebral transplantation; Neurodegenerative disorder; Parkinson's disease; Wnt/β-catenin