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

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 m...

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Main Authors: Wassim Altarche-Xifro, Umberto di Vicino, Maria Isabel Muñoz-Martin, Analía Bortolozzi, Jordi Bové, Miquel Vila, Maria Pia Cosma
Format: Article
Language:English
Published: Elsevier 2016-06-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396416301517
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spelling doaj-c0e012080bd1457eb636cddbb80db9c42020-11-24T21:47:05ZengElsevierEBioMedicine2352-39642016-06-018C839510.1016/j.ebiom.2016.04.016Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor CellsWassim Altarche-Xifro0Umberto di Vicino1Maria Isabel Muñoz-Martin2Analía Bortolozzi3Jordi Bové4Miquel Vila5Maria Pia Cosma6Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, SpainCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, SpainCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, SpainInstitut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, SpainNeurodegenerative Diseases Research Group, Vall d'Hebron Research Institute and Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, SpainNeurodegenerative Diseases Research Group, Vall d'Hebron Research Institute and Centre for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Barcelona, SpainCentre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, SpainParkinson'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.http://www.sciencedirect.com/science/article/pii/S2352396416301517Neurodegenerative disorderParkinson's diseaseHematopoietic stem and progenitor cellsCell fusionAstrogliaWnt/β-cateninIntracerebral transplantation
collection DOAJ
language English
format Article
sources DOAJ
author Wassim Altarche-Xifro
Umberto di Vicino
Maria Isabel Muñoz-Martin
Analía Bortolozzi
Jordi Bové
Miquel Vila
Maria Pia Cosma
spellingShingle Wassim Altarche-Xifro
Umberto di Vicino
Maria Isabel Muñoz-Martin
Analía Bortolozzi
Jordi Bové
Miquel Vila
Maria Pia Cosma
Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells
EBioMedicine
Neurodegenerative disorder
Parkinson's disease
Hematopoietic stem and progenitor cells
Cell fusion
Astroglia
Wnt/β-catenin
Intracerebral transplantation
author_facet Wassim Altarche-Xifro
Umberto di Vicino
Maria Isabel Muñoz-Martin
Analía Bortolozzi
Jordi Bové
Miquel Vila
Maria Pia Cosma
author_sort Wassim Altarche-Xifro
title Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells
title_short Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells
title_full Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells
title_fullStr Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells
title_full_unstemmed Functional Rescue of Dopaminergic Neuron Loss in Parkinson's Disease Mice After Transplantation of Hematopoietic Stem and Progenitor Cells
title_sort functional rescue of dopaminergic neuron loss in parkinson's disease mice after transplantation of hematopoietic stem and progenitor cells
publisher Elsevier
series EBioMedicine
issn 2352-3964
publishDate 2016-06-01
description 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.
topic Neurodegenerative disorder
Parkinson's disease
Hematopoietic stem and progenitor cells
Cell fusion
Astroglia
Wnt/β-catenin
Intracerebral transplantation
url http://www.sciencedirect.com/science/article/pii/S2352396416301517
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