Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts.

Autor:	Dulin JN; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA., Adler AF; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA., Kumamaru H; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA., Poplawski GHD; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA., Lee-Kubli C; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA., Strobl H; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA., Gibbs D; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA., Kadoya K; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.; Department of Orthopaedic Surgery, Hokkaido University, Sapporo, 060-8638, Japan., Fawcett JW; John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0SP, UK., Lu P; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA.; Veterans Administration Medical Center, San Diego, CA, 92161, USA., Tuszynski MH; Department of Neurosciences, University of California, San Diego, La Jolla, CA, 92093, USA. mtuszynski@ucsd.edu.; Veterans Administration Medical Center, San Diego, CA, 92161, USA. mtuszynski@ucsd.edu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2018 Jan 08; Vol. 9 (1), pp. 84. Date of Electronic Publication: 2018 Jan 08.
DOI:	10.1038/s41467-017-02613-x
Abstrakt:	Neural progenitor cell (NPC) transplantation has high therapeutic potential in neurological disorders. Functional restoration may depend on the formation of reciprocal connections between host and graft. While it has been reported that axons extending out of neural grafts in the brain form contacts onto phenotypically appropriate host target regions, it is not known whether adult, injured host axons regenerating into NPC grafts also form appropriate connections. We report that spinal cord NPCs grafted into the injured adult rat spinal cord self-assemble organotypic, dorsal horn-like domains. These clusters are extensively innervated by regenerating adult host sensory axons and are avoided by corticospinal axons. Moreover, host axon regeneration into grafts increases significantly after enrichment with appropriate neuronal targets. Together, these findings demonstrate that injured adult axons retain the ability to recognize appropriate targets and avoid inappropriate targets within neural progenitor grafts, suggesting that restoration of complex circuitry after SCI may be achievable.
Databáze:	MEDLINE
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