title: Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury.
abstract: 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.
authors.affiliation: Uppsala University, Department of Neuroscience, Husargatan 3, 75124 Uppsala, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Hoeber
authors.affiliation: Uppsala University, Department of Neuroscience, Husargatan 3, 75124 Uppsala, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Trolle
authors.affiliation: Uppsala University, Department of Neuroscience, Husargatan 3, 75124 Uppsala, Sweden.
authors.forename: Niclas
authors.initials: N
authors.lastname: Konig
authors.affiliation: Waisman Center, University of Wisconsin, 1500 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Du
authors.affiliation: Institute of Neuroscience, Université Catholique de Louvain, Avenue Hippocrate 54, 1200, Brussels, Belgium.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gallo
authors.affiliation: Institute of Neuroscience, Université Catholique de Louvain, Avenue Hippocrate 54, 1200, Brussels, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hermans
authors.affiliation: Uppsala University, Department of Neuroscience, Husargatan 3, 75124 Uppsala, Sweden.
authors.forename: Hakan
authors.initials: H
authors.lastname: Aldskogius
authors.affiliation: Medical Sciences, School of Science and Health, University of Western Sydney, Campbelltown Campus, Narellan Road, NSW 2567, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Shortland
authors.affiliation: Waisman Center, University of Wisconsin, 1500 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Su-Chun
authors.initials: SC
authors.lastname: Zhang
authors.affiliation: Institute of Neuroscience, Université Catholique de Louvain, Avenue Hippocrate 54, 1200, Brussels, Belgium.
authors.forename: Ronald
authors.initials: R
authors.lastname: Deumens
authors.affiliation: Uppsala University, Department of Neuroscience, Husargatan 3, 75124 Uppsala, Sweden.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Kozlova
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology; D000066449:Human Embryonic Stem Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D013126:Spinal Nerve Roots / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*