Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells
Altarche-Xifro, Wassim (Universitat Pompeu Fabra)
di Vicino, Umberto (Universitat Pompeu Fabra)
Muñoz-Martin, Maria Isabel (Universitat Pompeu Fabra)
Bortolozzi, Analía (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Bové, Jordi (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Vila Bover, Miquel (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Cosma, Maria Pia (Institució Catalana de Recerca i Estudis Avançats)
Universitat Autònoma de Barcelona

Fecha:	2016
Resumen:	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 4 weeks 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. A definitive therapy for Parkinson's disease is not available. Here, we transplanted hematopoietic stem and progenitor cells into the substantia nigra of brains of two different mouse models of Parkinson's disease. These transplanted cells fused with neurons and glial cells of the recipient mice. Four weeks after transplantation, the hybrids acquired features of mature astroglia, secreted Wnt1, and functionally ameliorated dopaminergic neuron loss. Current cell therapy approaches are being pursued in the striatum with the aim to increase dopamine levels. Here we show that the loss of dopaminergic neurons can be protected against by direct actions in the substantia nigra.
Ayudas:	Ministerio de Ciencia e Innovación SAF2011-28580 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1137 Ministerio de Ciencia e Innovación BFU2015-71984-ERC Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-780 Instituto de Salud Carlos III PI13-01897 Instituto de Salud Carlos III CP11-00229 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-1609 Ministerio de Economía y Competitividad SEV-2012-0208
Nota:	Altres ajuts: We are grateful for the support from a Fundació La Marató de TV3 grant (120530 to M.P.C. and M.V.), an ERC grant (242630-RERE to M.P.C.),European Union Seventh Framework Programme (FP7/2007-2013) under the Marie Curie IntraEuropean Fellowship (274882 to W.A.X). SEV-2012-0208.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Neurodegenerative disorder ; Parkinson's disease ; Hematopoietic stem and progenitor cells ; Cell fusion ; Astroglia ; Wnt/β-catenin ; Intracerebral transplantation
Publicado en:	EBioMedicine, Vol. 8 (april 2016) , p. 83-95, ISSN 2352-3964

DOI: 10.1016/j.ebiom.2016.04.016
PMID: 27428421

13 p, 3.4 MB

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