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

Jennifer N. Dulin, Andrew F. Adler, Hiromi Kumamaru, Gunnar H. D. Poplawski, Corinne Lee-Kubli, Hans Strobl, Daniel Gibbs, Ken Kadoya, James W. Fawcett, Paul Lu and Mark H. Tuszynski ()
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Jennifer N. Dulin: University of California, San Diego
Andrew F. Adler: University of California, San Diego
Hiromi Kumamaru: University of California, San Diego
Gunnar H. D. Poplawski: University of California, San Diego
Corinne Lee-Kubli: University of California, San Diego
Hans Strobl: University of California, San Diego
Daniel Gibbs: University of California, San Diego
Ken Kadoya: University of California, San Diego
James W. Fawcett: University of Cambridge
Paul Lu: University of California, San Diego
Mark H. Tuszynski: University of California, San Diego

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-017-02613-x

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