Journal article
Transplants of Neurotrophin-Producing Autologous Fibroblasts Promote Recovery of Treadmill Stepping in the Acute, Sub-Chronic, and Chronic Spinal Cat
Journal of neurotrauma, v 34(10), pp 1858-1872
15 May 2017
PMID: 27829315
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Adult cats show limited spontaneous locomotor capabilities following spinal transection, but recover treadmill stepping with body-weight-supported training. Delivery of neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and neurotrophic factor 3 (NT-3) can substitute for body-weight-supported training, and promotes a similar recovery in a shorter period of time. Autologous cell grafts would negate the need for the immunosuppressive agents currently used with most grafts, but have not shown functional benefits in incomplete spinal cord injury models and have never been tested in complete transection or chronic injury models. In this study, we explored the effects of autologous fibroblasts, prepared from the individual cats and modified to produce BDNF and NT-3, on the recovery of locomotion in acute, sub-chronic and chronic full-transection models of spinal injury. Fourteen female cats underwent complete spinal transection at T11/T12. Cats were separated into four groups: sham graft at the time of injury, and BDNF and NT-3 producing autologous fibroblasts grafted at the time of injury, 2 weeks after injury, or 6 weeks after injury. Kinematics were recorded 3 and 5 weeks after cell graft. Additional kinematic recordings were taken for some cats until 12 weeks post-graft. Eleven of 12 cats with neurotrophin-producing grafts recovered plantar weight-bearing stepping at treadmill speeds from 0.3 to 0.8m/sec within 5 weeks of grafting, whereas control cats recovered poor quality stepping at low speeds only ( 0.4m/sec). Further, kinematic measures in cats with grafts were closer to pre-transection values than those for controls, and recovery was maintained up to 12 weeks post-grafting. Our results show that not only are autologous neurotrophin-producing grafts effective at promoting recovery of locomotion, but that delayed delivery of neurotrophins does not diminish the therapeutic effect, and may improve outcome.
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Details
- Title
- Transplants of Neurotrophin-Producing Autologous Fibroblasts Promote Recovery of Treadmill Stepping in the Acute, Sub-Chronic, and Chronic Spinal Cat
- Creators
- Alexander J. Krupka - Temple UniversityItzhak Fischer - Drexel UniversityMichel A. Lemay - Temple University
- Publication Details
- Journal of neurotrauma, v 34(10), pp 1858-1872
- Publisher
- Mary Ann Liebert, Inc
- Number of pages
- 15
- Grant note
- NIH EB012855 / National Institute of Biomedical Imaging and Bioengineering; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) NIH NS074406 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R01EB012855 / NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) R01NS074406 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000400989900003
- Scopus ID
- 2-s2.0-85019176938
- Other Identifier
- 991019168130704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Clinical Neurology
- Critical Care Medicine
- Neurosciences