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Title

Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells

AuthorsAltarche-Xifro, Wassim; di Vicino, Umberto; Muñoz-Martín, María Isabel; Bortolozzi, Analía ; Bové, Jordi; Vila, M.; Cosma, María Pía
KeywordsNeurodegenerative disorder
Intracerebral transplantation
Wnt/β-catenin
Astroglia
Cell fusion
Hematopoietic stem and progenitor cells
Parkinson's disease
Issue DateJun-2016
PublisherElsevier
CitationEBioMedicine 8: 83-95 (2016)
AbstractParkinson'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.
Publisher version (URL)https://doi.org/10.1016/j.ebiom.2016.04.016
URIhttp://hdl.handle.net/10261/148626
DOIhttp://dx.doi.org/10.1016/j.ebiom.2016.04.016
Identifiersdoi: 10.1016/j.ebiom.2016.04.016
issn: 2352-3964
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