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Stem Cell Reports. 2019 Jul 9;13(1):105-114. doi: 10.1016/j.stemcr.2019.05.011. Epub 2019 Jun 13.

Origins of Neural Progenitor Cell-Derived Axons Projecting Caudally after Spinal Cord Injury.

Author information

1
Veterans Administration-San Diego Healthcare System, San Diego, CA 92161, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0626, USA. Electronic address: plu@ucsd.edu.
2
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0626, USA; Laboratory of Experimental Neuroprotection and Neuroregeneration, Institute of Biological Sciences, Federal University of Pará Belém, Brazil.
3
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0626, USA; Center for Neuroprosthetics and Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Geneva, Switzerland.
4
Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0626, USA.
5
Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
6
Veterans Administration-San Diego Healthcare System, San Diego, CA 92161, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093-0626, USA. Electronic address: mtuszynski@ucsd.edu.

Abstract

Neural progenitor cells (NPCs) transplanted into sites of spinal cord injury (SCI) extend large numbers of axons into the caudal host spinal cord. We determined the precise locations of neurons in the graft that extend axons into the caudal host spinal cord using AAV9-Cre-initiated retrograde tracing into floxed-TdTomato-expressing NPC grafts. 7,640 ± 630 grafted neurons extended axons to a single caudal host spinal cord site located 2 mm beyond the lesion, 5 weeks post injury. While caudally projecting axons arose from neurons located in all regions of the graft, the majority of caudally projecting graft neurons (53%) were located within the caudal one-third of the graft. Numerous host corticospinal axons formed monosynaptic projections onto caudally projecting graft neurons; however, we find that the majority of host axonal neuronal projections formed by neural progenitor cell interneuronal "relays" across sites of SCI are likely polysynaptic in nature.

KEYWORDS:

axonal growth; axonal regeneration; neural progenitor cells; neural stem cells; spinal cord injury

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