Journal article
Transplantation of Human Glial Restricted Progenitors and Derived Astrocytes into a Contusion Model of Spinal Cord Injury
Journal of neurotrauma, v 28(4), pp 579-594
01 Apr 2011
PMID: 21222572
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Transplantation of neural progenitors remains a promising therapeutic approach to spinal cord injury (SCI), but the anatomical and functional evaluation of their effects is complex, particularly when using human cells. We investigated the outcome of transplanting human glial-restricted progenitors (hGRP) and astrocytes derived from hGRP (hGDA) in spinal cord contusion with respect to cell fate and host response using athymic rats to circumvent xenograft immune issues. Nine days after injury hGRP, hGDA, or medium were injected into the lesion center and rostral and caudal to the lesion, followed by behavioral testing for 8 weeks. Both hGRP and hGDA showed robust graft survival and extensive migration. The total number of cells increased 3.5-fold for hGRP, and twofold for hGDA, indicating graft expansion, but few proliferating cells remained by 8 weeks. Grafted cells differentiated into glia, predominantly astrocytes, and few remained at progenitor state. About 80% of grafted cells around the injury were glial fibrillary acidic protein (GFAP)-positive, gradually decreasing to 40–50% at a distance of 6 mm. Conversely, there were few graft-derived oligodendrocytes at the lesion, but their numbers increased away from the injury to 30–40%. Both cell grafts reduced cyst and scar formation at the injury site compared to controls. Microglia/macrophages were present at and around the lesion area, and axons grew along the spared tissue with no differences among groups. There were no significant improvements in motor function recovery as measured by the Basso, Beattie, and Bresnahan (BBB) scale and grid tests in all experimental groups. Cystometry revealed that hGRP grafts attenuated hyperactive bladder reflexes. Importantly, there was no increased sensory or tactile sensitivity associated with pain, and the hGDA group showed sensory function returning to normal. Although the improved lesion environment was not sufficient for robust functional recovery, the permissive properties and lack of sensory hypersensitivity indicate that human GRP and astrocytes remain promising candidates for therapy after SCI.
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Details
- Title
- Transplantation of Human Glial Restricted Progenitors and Derived Astrocytes into a Contusion Model of Spinal Cord Injury
- Creators
- Ying Jin - 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaBirgit Neuhuber - 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaAnita Singh - 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaJulien Bouyer - 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaAngelo Lepore - 2Department of Neuroscience, Thomas Jefferson Medical College, Philadelphia, PennsylveniaJoseph Bonner - 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaTim Himes - 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PennsylvaniaJames T Campanelli - 3Q Therapeutics, Inc., Salt Lake City, UtahItzhak Fischer - 1Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania
- Publication Details
- Journal of neurotrauma, v 28(4), pp 579-594
- Publisher
- Mary Ann Liebert, Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000289240200008
- Scopus ID
- 2-s2.0-79953833683
- Other Identifier
- 991014877911404721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences