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Journal article
Transplantation of Neural Progenitors and V2a Interneurons after Spinal Cord Injury
Journal of neurotrauma, v 35(24), pp 2883-2903
13 Dec 2018
PMID: 29873284
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
There is growing interest in the use of neural precursor cells to treat spinal cord injury (SCI). Despite extensive pre-clinical research, it remains unclear as to which donor neuron phenotypes are available for transplantation, whether the same populations exist across different sources of donor tissue (e.g., developing tissue vs. cultured cells), and whether donor cells retain their phenotype once transplanted into the hostile internal milieu of the injured adult spinal cord. In addition, while functional improvements have been reported after neural precursor transplantation post-SCI, the extent of recovery is limited and variable. The present work begins to address these issues by harnessing ventrally derived excitatory pre-motor V2a spinal interneurons (SpINs) to repair the phrenic motor circuit after cervical SCI. Recent studies have demonstrated that Chx10-positive V2a SpINs contribute to anatomical plasticity within the phrenic circuitry after cervical SCI, thus identifying them as a therapeutic candidate. Building upon this discovery, the present work tests the hypothesis that transplantation of neural progenitor cells (NPCs) enriched with V2a INs can contribute to neural networks that promote repair and enhance respiratory plasticity after cervical SCI. Cultured NPCs (neuronal and glial restricted progenitor cells) isolated from E13.5 Green fluorescent protein rats were aggregated with TdTomato-mouse embryonic stem cell–derived V2a INs
in vitro
, then transplanted into the injured cervical (C3-4) spinal cord. Donor cells survive, differentiate and integrate with the host spinal cord. Functional diaphragm electromyography indicated recovery 1 month following treatment in transplant recipients. Animals that received donor cells enriched with V2a INs showed significantly greater functional improvement than animals that received NPCs alone. The results from this study offer insight into the neuronal phenotypes that might be effective for (re)establishing neuronal circuits in the injured adult central nervous system.
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Details
- Title
- Transplantation of Neural Progenitors and V2a Interneurons after Spinal Cord Injury
- Creators
- Lyandysha V. Zholudeva - Drexel UniversityNisha Iyer - Wisconsin Institutes for DiscoveryLiang Qiang - Drexel UniversityVictoria M. Spruance - Drexel UniversityMargo L. Randelman - Drexel UniversityNicholas W. White - 4Department of Biomedical Engineering, University of Texas, Austin, TexasTatiana Bezdudnaya - Drexel UniversityItzhak Fischer - Drexel UniversityShelly E. Sakiyama-Elbert - The University of Texas at AustinMichael A. Lane - Drexel University
- Publication Details
- Journal of neurotrauma, v 35(24), pp 2883-2903
- Publisher
- Mary Ann Liebert, Inc., publishers
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000453695000003
- Scopus ID
- 2-s2.0-85051574999
- Other Identifier
- 991019168274704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences