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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/6/5575 |
| _version_ | 1797611226160693248 |
|---|---|
| author | Javier Villadiego Ana B. Muñoz-Manchado Verónica Sobrino Victoria Bonilla-Henao Nela Suárez-Luna Patricia Ortega-Sáenz Ricardo Pardal José López-Barneo Juan J. Toledo-Aral |
| author_facet | Javier Villadiego Ana B. Muñoz-Manchado Verónica Sobrino Victoria Bonilla-Henao Nela Suárez-Luna Patricia Ortega-Sáenz Ricardo Pardal José López-Barneo Juan J. Toledo-Aral |
| author_sort | Javier Villadiego |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T06:25:52Z |
| format | Article |
| id | doaj.art-3449550320e44403a6f0c31d50244dfb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:25:52Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3449550320e44403a6f0c31d50244dfb2023-11-17T11:35:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246557510.3390/ijms24065575Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian ModelJavier Villadiego0Ana B. Muñoz-Manchado1Verónica Sobrino2Victoria Bonilla-Henao3Nela Suárez-Luna4Patricia Ortega-Sáenz5Ricardo Pardal6José López-Barneo7Juan J. Toledo-Aral8Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, SpainUnidad de Biología Celular, Departamento de Anatomía Patológica, Biología Celular, Histología, Historia de la Ciencia, Medicina Legal y Forense y Toxicología, INiBICA (Instituto de Investigación e Innovación Biomédica de Cádiz), Universidad de Cádiz, 11003 Cádiz, SpainInstituto Maimónides de Investigación Biomédica de Córdoba, Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, 14004 Córdoba, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, SpainInstituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, SpainAntiparkinsonian 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.https://www.mdpi.com/1422-0067/24/6/5575Parkinson’s diseasecell therapycarotid body stem cellsneuroprotectionneurorestoration |
| spellingShingle | Javier Villadiego Ana B. Muñoz-Manchado Verónica Sobrino Victoria Bonilla-Henao Nela Suárez-Luna Patricia Ortega-Sáenz Ricardo Pardal José López-Barneo Juan J. Toledo-Aral Protection and Repair of the Nigrostriatal Pathway with Stem-Cell-Derived Carotid Body Glomus Cell Transplants in Chronic MPTP Parkinsonian Model International Journal of Molecular Sciences Parkinson’s disease cell therapy carotid body stem cells neuroprotection neurorestoration |
| 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 | Parkinson’s disease cell therapy carotid body stem cells neuroprotection neurorestoration |
| url | https://www.mdpi.com/1422-0067/24/6/5575 |
| work_keys_str_mv | AT javiervilladiego protectionandrepairofthenigrostriatalpathwaywithstemcellderivedcarotidbodyglomuscelltransplantsinchronicmptpparkinsonianmodel AT anabmunozmanchado protectionandrepairofthenigrostriatalpathwaywithstemcellderivedcarotidbodyglomuscelltransplantsinchronicmptpparkinsonianmodel AT veronicasobrino protectionandrepairofthenigrostriatalpathwaywithstemcellderivedcarotidbodyglomuscelltransplantsinchronicmptpparkinsonianmodel AT victoriabonillahenao protectionandrepairofthenigrostriatalpathwaywithstemcellderivedcarotidbodyglomuscelltransplantsinchronicmptpparkinsonianmodel AT nelasuarezluna protectionandrepairofthenigrostriatalpathwaywithstemcellderivedcarotidbodyglomuscelltransplantsinchronicmptpparkinsonianmodel AT patriciaortegasaenz protectionandrepairofthenigrostriatalpathwaywithstemcellderivedcarotidbodyglomuscelltransplantsinchronicmptpparkinsonianmodel AT ricardopardal protectionandrepairofthenigrostriatalpathwaywithstemcellderivedcarotidbodyglomuscelltransplantsinchronicmptpparkinsonianmodel AT joselopezbarneo protectionandrepairofthenigrostriatalpathwaywithstemcellderivedcarotidbodyglomuscelltransplantsinchronicmptpparkinsonianmodel AT juanjtoledoaral protectionandrepairofthenigrostriatalpathwaywithstemcellderivedcarotidbodyglomuscelltransplantsinchronicmptpparkinsonianmodel |