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Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model

Antiparkinsonian carotid body (CB) cell therapy has been proven to be effective in rodent and nonhuman primate models of Parkinson’s disease (PD), exerting trophic protection and restoration of the dopaminergic nigrostriatal pathway. These neurotrophic actions are mediated through the release of hig...

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Autores principales: Villadiego, Javier, Muñoz-Manchado, Ana B., Sobrino, Verónica, Bonilla-Henao, Victoria, Suárez-Luna, Nela, Ortega-Sáenz, Patricia, Pardal, Ricardo, López-Barneo, José, Toledo-Aral, Juan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057403/
https://www.ncbi.nlm.nih.gov/pubmed/36982650
http://dx.doi.org/10.3390/ijms24065575
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author Villadiego, Javier
Muñoz-Manchado, Ana B.
Sobrino, Verónica
Bonilla-Henao, Victoria
Suárez-Luna, Nela
Ortega-Sáenz, Patricia
Pardal, Ricardo
López-Barneo, José
Toledo-Aral, Juan J.
author_facet Villadiego, Javier
Muñoz-Manchado, Ana B.
Sobrino, Verónica
Bonilla-Henao, Victoria
Suárez-Luna, Nela
Ortega-Sáenz, Patricia
Pardal, Ricardo
López-Barneo, José
Toledo-Aral, Juan J.
author_sort Villadiego, Javier
collection PubMed
description Antiparkinsonian carotid body (CB) cell therapy has been proven to be effective in rodent and nonhuman primate models of Parkinson’s disease (PD), exerting trophic protection and restoration of the dopaminergic nigrostriatal pathway. These neurotrophic actions are mediated through the release of high levels of glial-cell-line-derived neurotrophic factor (GDNF) by the CB transplant. Pilot clinical trials have also shown that CB autotransplantation can improve motor symptoms in PD patients, although its effectiveness is affected by the scarcity of the grafted tissue. Here, we analyzed the antiparkinsonian efficacy of in vitro-expanded CB dopaminergic glomus cells. Intrastriatal xenografts of rat CB neurospheres were shown to protect nigral neurons from degeneration in a chronic MPTP mouse PD model. In addition, grafts performed at the end of the neurotoxic treatment resulted in the repair of striatal dopaminergic terminals through axonal sprouting. Interestingly, both neuroprotective and reparative effects induced by in vitro-expanded CB cells were similar to those previously reported by the use of CB transplants. This action could be explained because stem-cell-derived CB neurospheres produce similar amounts of GDNF compared to native CB tissue. This study provides the first evidence that in vitro-expanded CB cells could be a clinical option for cell therapy in PD.
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spelling pubmed-100574032023-03-30 Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model Villadiego, Javier Muñoz-Manchado, Ana B. Sobrino, Verónica Bonilla-Henao, Victoria Suárez-Luna, Nela Ortega-Sáenz, Patricia Pardal, Ricardo López-Barneo, José Toledo-Aral, Juan J. Int J Mol Sci Communication Antiparkinsonian carotid body (CB) cell therapy has been proven to be effective in rodent and nonhuman primate models of Parkinson’s disease (PD), exerting trophic protection and restoration of the dopaminergic nigrostriatal pathway. These neurotrophic actions are mediated through the release of high levels of glial-cell-line-derived neurotrophic factor (GDNF) by the CB transplant. Pilot clinical trials have also shown that CB autotransplantation can improve motor symptoms in PD patients, although its effectiveness is affected by the scarcity of the grafted tissue. Here, we analyzed the antiparkinsonian efficacy of in vitro-expanded CB dopaminergic glomus cells. Intrastriatal xenografts of rat CB neurospheres were shown to protect nigral neurons from degeneration in a chronic MPTP mouse PD model. In addition, grafts performed at the end of the neurotoxic treatment resulted in the repair of striatal dopaminergic terminals through axonal sprouting. Interestingly, both neuroprotective and reparative effects induced by in vitro-expanded CB cells were similar to those previously reported by the use of CB transplants. This action could be explained because stem-cell-derived CB neurospheres produce similar amounts of GDNF compared to native CB tissue. This study provides the first evidence that in vitro-expanded CB cells could be a clinical option for cell therapy in PD. MDPI 2023-03-14 /pmc/articles/PMC10057403/ /pubmed/36982650 http://dx.doi.org/10.3390/ijms24065575 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Villadiego, Javier
Muñoz-Manchado, Ana B.
Sobrino, Verónica
Bonilla-Henao, Victoria
Suárez-Luna, Nela
Ortega-Sáenz, Patricia
Pardal, Ricardo
López-Barneo, José
Toledo-Aral, Juan J.
Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model
title Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model
title_full Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model
title_fullStr Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model
title_full_unstemmed Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model
title_short Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model
title_sort protection and repair of the nigrostriatal pathway with stem-cell-derived carotid body glomus cell transplants in chronic mptp parkinsonian model
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057403/
https://www.ncbi.nlm.nih.gov/pubmed/36982650
http://dx.doi.org/10.3390/ijms24065575
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