An In Vivo Platform for Rebuilding Functional Neocortical Tissue
Recent progress in cortical stem cell transplantation has demonstrated its potential to repair the brain. However, current transplant models have yet to demonstrate that the circuitry of transplant-derived neurons can encode useful function to the host. This is likely due to missing cell types withi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/10/2/263 |
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| author | Alexandra Quezada Claire Ward Edward R. Bader Pavlo Zolotavin Esra Altun Sarah Hong Nathaniel J. Killian Chong Xie Renata Batista-Brito Jean M. Hébert |
| author_facet | Alexandra Quezada Claire Ward Edward R. Bader Pavlo Zolotavin Esra Altun Sarah Hong Nathaniel J. Killian Chong Xie Renata Batista-Brito Jean M. Hébert |
| author_sort | Alexandra Quezada |
| collection | DOAJ |
| description | Recent progress in cortical stem cell transplantation has demonstrated its potential to repair the brain. However, current transplant models have yet to demonstrate that the circuitry of transplant-derived neurons can encode useful function to the host. This is likely due to missing cell types within the grafts, abnormal proportions of cell types, abnormal cytoarchitecture, and inefficient vascularization. Here, we devised a transplant platform for testing neocortical tissue prototypes. Dissociated mouse embryonic telencephalic cells in a liquid scaffold were transplanted into aspiration-lesioned adult mouse cortices. The donor neuronal precursors differentiated into upper and deep layer neurons that exhibited synaptic puncta, projected outside of the graft to appropriate brain areas, became electrophysiologically active within one month post-transplant, and responded to visual stimuli. Interneurons and oligodendrocytes were present at normal densities in grafts. Grafts became fully vascularized by one week post-transplant and vessels in grafts were perfused with blood. With this paradigm, we could also organize cells into layers. Overall, we have provided proof of a concept for an in vivo platform that can be used for developing and testing neocortical-like tissue prototypes. |
| first_indexed | 2024-03-11T09:07:53Z |
| format | Article |
| id | doaj.art-40d430e4cb694eeba6503b6719224c82 |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-11T09:07:53Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-40d430e4cb694eeba6503b6719224c822023-11-16T19:11:58ZengMDPI AGBioengineering2306-53542023-02-0110226310.3390/bioengineering10020263An In Vivo Platform for Rebuilding Functional Neocortical TissueAlexandra Quezada0Claire Ward1Edward R. Bader2Pavlo Zolotavin3Esra Altun4Sarah Hong5Nathaniel J. Killian6Chong Xie7Renata Batista-Brito8Jean M. Hébert9Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Neurological Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Electrical and Computer Engineering, Rice University, Houston, TX 77005, USADepartment of Electrical and Computer Engineering, Rice University, Houston, TX 77005, USADepartment of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Neurological Surgery, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Electrical and Computer Engineering, Rice University, Houston, TX 77005, USADepartment of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USADepartment of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USARecent progress in cortical stem cell transplantation has demonstrated its potential to repair the brain. However, current transplant models have yet to demonstrate that the circuitry of transplant-derived neurons can encode useful function to the host. This is likely due to missing cell types within the grafts, abnormal proportions of cell types, abnormal cytoarchitecture, and inefficient vascularization. Here, we devised a transplant platform for testing neocortical tissue prototypes. Dissociated mouse embryonic telencephalic cells in a liquid scaffold were transplanted into aspiration-lesioned adult mouse cortices. The donor neuronal precursors differentiated into upper and deep layer neurons that exhibited synaptic puncta, projected outside of the graft to appropriate brain areas, became electrophysiologically active within one month post-transplant, and responded to visual stimuli. Interneurons and oligodendrocytes were present at normal densities in grafts. Grafts became fully vascularized by one week post-transplant and vessels in grafts were perfused with blood. With this paradigm, we could also organize cells into layers. Overall, we have provided proof of a concept for an in vivo platform that can be used for developing and testing neocortical-like tissue prototypes.https://www.mdpi.com/2306-5354/10/2/263neocortextransplanttissue replacementvascularizationlayering |
| spellingShingle | Alexandra Quezada Claire Ward Edward R. Bader Pavlo Zolotavin Esra Altun Sarah Hong Nathaniel J. Killian Chong Xie Renata Batista-Brito Jean M. Hébert An In Vivo Platform for Rebuilding Functional Neocortical Tissue Bioengineering neocortex transplant tissue replacement vascularization layering |
| title | An In Vivo Platform for Rebuilding Functional Neocortical Tissue |
| title_full | An In Vivo Platform for Rebuilding Functional Neocortical Tissue |
| title_fullStr | An In Vivo Platform for Rebuilding Functional Neocortical Tissue |
| title_full_unstemmed | An In Vivo Platform for Rebuilding Functional Neocortical Tissue |
| title_short | An In Vivo Platform for Rebuilding Functional Neocortical Tissue |
| title_sort | in vivo platform for rebuilding functional neocortical tissue |
| topic | neocortex transplant tissue replacement vascularization layering |
| url | https://www.mdpi.com/2306-5354/10/2/263 |
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