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Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury.

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Hoeber, Jan Trolle, Carl Konig, Niclas Du, Zhongwei Gallo, Alessandro [UCL] Hermans, Emmanuel [UCL] Deumens, Ronald [UCL] Kozlova, Elena N

Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 2015
Language Anglais
Journal information "Scientific Reports" - Vol. 5, p. 10666 (2015)
Peer reviewed yes
Publisher Nature Publishing Group (London)
issn 2045-2322
e-issn 2045-2322
Publication status Publié
Affiliation UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire
Links
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Bibliographic reference Hoeber, Jan ; Trolle, Carl ; Konig, Niclas ; Du, Zhongwei ; Gallo, Alessandro ; et. al. Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury.. In: Scientific Reports, Vol. 5, p. 10666 (2015)
Permanent URL http://hdl.handle.net/2078.1/162474