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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2016-06-01
|
Series: | EBioMedicine |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396416301517 |
id |
doaj-c0e012080bd1457eb636cddbb80db9c4 |
---|---|
record_format |
Article |
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 |
work_keys_str_mv |
AT wassimaltarchexifro functionalrescueofdopaminergicneuronlossinparkinsonsdiseasemiceaftertransplantationofhematopoieticstemandprogenitorcells AT umbertodivicino functionalrescueofdopaminergicneuronlossinparkinsonsdiseasemiceaftertransplantationofhematopoieticstemandprogenitorcells AT mariaisabelmunozmartin functionalrescueofdopaminergicneuronlossinparkinsonsdiseasemiceaftertransplantationofhematopoieticstemandprogenitorcells AT analiabortolozzi functionalrescueofdopaminergicneuronlossinparkinsonsdiseasemiceaftertransplantationofhematopoieticstemandprogenitorcells AT jordibove functionalrescueofdopaminergicneuronlossinparkinsonsdiseasemiceaftertransplantationofhematopoieticstemandprogenitorcells AT miquelvila functionalrescueofdopaminergicneuronlossinparkinsonsdiseasemiceaftertransplantationofhematopoieticstemandprogenitorcells AT mariapiacosma functionalrescueofdopaminergicneuronlossinparkinsonsdiseasemiceaftertransplantationofhematopoieticstemandprogenitorcells |
_version_ |
1725899543369744384 |