Regeneration of adult rat sensory and motor neuron axons through chimeric peroneal nerve grafts containing donor Schwann cells engineered to express different neurotrophic factors.
Autor: | Godinho MJ; School of Human Sciences, The University of Western Australia, Crawley, WA 6009, Australia., Staal JL; School of Human Sciences, The University of Western Australia, Crawley, WA 6009, Australia., Krishnan VS; School of Human Sciences, The University of Western Australia, Crawley, WA 6009, Australia., Hodgetts SI; School of Human Sciences, The University of Western Australia, Crawley, WA 6009, Australia; Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia., Pollett MA; School of Human Sciences, The University of Western Australia, Crawley, WA 6009, Australia., Goodman DP; School of Veterinary and Biomedical Sciences, Murdoch University, Murdoch, WA 6150, Australia., Teh L; Plastic Surgery Centre, St John of God Hospital, Murdoch, WA 6150, Australia., Verhaagen J; Netherlands Institute for Neuroscience, Meibergdreef 47, Amsterdam, the Netherlands., Plant GW; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA., Harvey AR; School of Human Sciences, The University of Western Australia, Crawley, WA 6009, Australia; Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia. Electronic address: alan.harvey@uwa.edu.au. |
---|---|
Jazyk: | angličtina |
Zdroj: | Experimental neurology [Exp Neurol] 2020 Aug; Vol. 330, pp. 113355. Date of Electronic Publication: 2020 May 15. |
DOI: | 10.1016/j.expneurol.2020.113355 |
Abstrakt: | Large peripheral nerve (PN) defects require bridging substrates to restore tissue continuity and permit the regrowth of sensory and motor axons. We previously showed that cell-free PN segments repopulated ex vivo with Schwann cells (SCs) transduced with lentiviral vectors (LV) to express different growth factors (BDNF, CNTF or NT-3) supported the regeneration of axons across a 1 cm peroneal nerve defect (Godinho et al., 2013). Graft morphology, the number of regrown axons, the ratio of myelinated to unmyelinated axons, and hindlimb locomotor function differed depending on the growth factor engineered into SCs. Here we extend these observations, adding more LVs (expressing GDNF or NGF) and characterising regenerating sensory and motor neurons after injection of the retrograde tracer Fluorogold (FG) into peroneal nerve distal to grafts, 10 weeks after surgery. Counts were also made in rats with intact nerves and in animals receiving autografts, acellular grafts, or grafts containing LV-GFP transduced SCs. Counts and analysis of FG positive ( + ) DRG neurons were made from lumbar (L5) ganglia. Graft groups contained fewer labeled sensory neurons than non-operated controls, but this decrease was only significant in the LV-GDNF group. These grafts had a complex fascicular morphology that may have resulted in axon trapping. The proportion of FG + sensory neurons immunopositive for calcitonin-gene related peptide (CGRP) varied between groups, there being a significantly higher percentage in autografts and most neurotrophic factor groups compared to the LV-CNTF, LV-GFP and acellular groups. Furthermore, the proportion of regenerating isolectin B (Copyright © 2020 Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
Externí odkaz: |