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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

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

International journal of molecular sciences, 2023-03, Vol.24 (6), p.5575 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model
Autor: 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
Assuntos: Analysis ; Animal models ; Animals ; Axon sprouting ; Basal ganglia ; Carotid body ; Carotid Body - metabolism ; carotid body stem cells ; Cell therapy ; Cell Transplantation ; Central nervous system diseases ; Clinical trials ; Communication ; Corpus Striatum - metabolism ; Degeneration ; Disease Models, Animal ; Dopamine ; Dopamine - metabolism ; Dopamine receptors ; Dopaminergic Neurons - metabolism ; Glial cell line-derived neurotrophic factor ; Glial Cell Line-Derived Neurotrophic Factor - metabolism ; Glomus cells ; Humans ; Hypoxia ; Mice ; MPTP ; Neostriatum ; Neuronal-glial interactions ; Neuroprotection ; neurorestoration ; Neurospheres ; Neurotoxicity ; Neurotrophic factors ; Parkinson Disease - metabolism ; Parkinson Disease - therapy ; Parkinson's disease ; Protection and preservation ; Rats ; Signs and symptoms ; Stem cells ; Substantia nigra ; Substantia Nigra - metabolism ; Transplantation ; Transplants ; Transplants & implants ; Xenografts ; Xenotransplantation
É parte de: International journal of molecular sciences, 2023-03, Vol.24 (6), p.5575
Notas: ObjectType-Article-1
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These authors contributed equally to this work.
Descrição: 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.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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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

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

Switzerland: MDPI AG

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