Transplantable human motor networks as a neuron-directed strategy for spinal cord injury
Summary: To repair neural circuitry following spinal cord injury (SCI), neural stem cell (NSC) transplantation has held a primary focus; however, stochastic outcomes generate challenges driven in part by NSC differentiation and tumor formation. The recent ability to generate regionally specific neur...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004221007951 |
| _version_ | 1818611646041423872 |
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| author | Zachary T. Olmsted Cinzia Stigliano Annalisa Scimemi Tatiana Wolfe Jose Cibelli Philip J. Horner Janet L. Paluh |
| author_facet | Zachary T. Olmsted Cinzia Stigliano Annalisa Scimemi Tatiana Wolfe Jose Cibelli Philip J. Horner Janet L. Paluh |
| author_sort | Zachary T. Olmsted |
| collection | DOAJ |
| description | Summary: To repair neural circuitry following spinal cord injury (SCI), neural stem cell (NSC) transplantation has held a primary focus; however, stochastic outcomes generate challenges driven in part by NSC differentiation and tumor formation. The recent ability to generate regionally specific neurons and their support cells now allows consideration of directed therapeutic approaches with pre-differentiated and networked spinal neural cells. Here, we form encapsulated, transplantable neuronal networks of regionally matched cervical spinal motor neurons, interneurons, and oligodendrocyte progenitor cells derived through trunk-biased neuromesodermal progenitors. We direct neurite formation in alginate-based neural ribbons to generate electrically active, synaptically connected networks, characterized by electrophysiology and calcium imaging before transplantation into rodent models of contused SCI for evaluation at 10-day and 6-week timepoints. The in vivo analyses demonstrate viability and retention of interconnected synaptic networks that readily integrate with the host parenchyma to advance goals of transplantable neural circuitry for SCI treatment. |
| first_indexed | 2024-12-16T15:33:38Z |
| format | Article |
| id | doaj.art-fa4b4b0469034dc28a0d1688b916eb29 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-16T15:33:38Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-fa4b4b0469034dc28a0d1688b916eb292022-12-21T22:26:16ZengElsevieriScience2589-00422021-08-01248102827Transplantable human motor networks as a neuron-directed strategy for spinal cord injuryZachary T. Olmsted0Cinzia Stigliano1Annalisa Scimemi2Tatiana Wolfe3Jose Cibelli4Philip J. Horner5Janet L. Paluh6State University of New York Polytechnic Institute, College of Nanoscale Science and Engineering, Nanobioscience Constellation, 257 Fuller Road, Albany, NY 12203, USAHouston Methodist Research Institute, Department of Neurosurgery, Center for Neuroregeneration, 6670 Bertner Avenue R10-North, Houston, TX 77030, USAState University of New York at Albany, Biological Sciences, 1400 Washington Avenue, Albany, NY 12222, USAHouston Methodist Research Institute, Department of Neurosurgery, Center for Neuroregeneration, 6670 Bertner Avenue R10-North, Houston, TX 77030, USAMichigan State University, Department of Animal Science, College of Agriculture and Natural Resources and Large Animal Clinical Sciences, College of Veterinary Medicine, East Lansing, MI48824, USAHouston Methodist Research Institute, Department of Neurosurgery, Center for Neuroregeneration, 6670 Bertner Avenue R10-North, Houston, TX 77030, USAState University of New York Polytechnic Institute, College of Nanoscale Science and Engineering, Nanobioscience Constellation, 257 Fuller Road, Albany, NY 12203, USA; Corresponding authorSummary: To repair neural circuitry following spinal cord injury (SCI), neural stem cell (NSC) transplantation has held a primary focus; however, stochastic outcomes generate challenges driven in part by NSC differentiation and tumor formation. The recent ability to generate regionally specific neurons and their support cells now allows consideration of directed therapeutic approaches with pre-differentiated and networked spinal neural cells. Here, we form encapsulated, transplantable neuronal networks of regionally matched cervical spinal motor neurons, interneurons, and oligodendrocyte progenitor cells derived through trunk-biased neuromesodermal progenitors. We direct neurite formation in alginate-based neural ribbons to generate electrically active, synaptically connected networks, characterized by electrophysiology and calcium imaging before transplantation into rodent models of contused SCI for evaluation at 10-day and 6-week timepoints. The in vivo analyses demonstrate viability and retention of interconnected synaptic networks that readily integrate with the host parenchyma to advance goals of transplantable neural circuitry for SCI treatment.http://www.sciencedirect.com/science/article/pii/S2589004221007951NeuroscienceBioengineeringTissue engineering |
| spellingShingle | Zachary T. Olmsted Cinzia Stigliano Annalisa Scimemi Tatiana Wolfe Jose Cibelli Philip J. Horner Janet L. Paluh Transplantable human motor networks as a neuron-directed strategy for spinal cord injury iScience Neuroscience Bioengineering Tissue engineering |
| title | Transplantable human motor networks as a neuron-directed strategy for spinal cord injury |
| title_full | Transplantable human motor networks as a neuron-directed strategy for spinal cord injury |
| title_fullStr | Transplantable human motor networks as a neuron-directed strategy for spinal cord injury |
| title_full_unstemmed | Transplantable human motor networks as a neuron-directed strategy for spinal cord injury |
| title_short | Transplantable human motor networks as a neuron-directed strategy for spinal cord injury |
| title_sort | transplantable human motor networks as a neuron directed strategy for spinal cord injury |
| topic | Neuroscience Bioengineering Tissue engineering |
| url | http://www.sciencedirect.com/science/article/pii/S2589004221007951 |
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