title: Murine neural crest stem cells and embryonic stem cell-derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion.
abstract: Spinal root avulsion results in paralysis and sensory loss, and is commonly associated with chronic pain. In addition to the failure of avulsed dorsal root axons to regenerate into the spinal cord, avulsion injury leads to extensive neuroinflammation and degeneration of second-order neurons in the dorsal horn. The ultimate objective in the treatment of this condition is to counteract degeneration of spinal cord neurons and to achieve functionally useful regeneration/reconnection of sensory neurons with spinal cord neurons. Here we compare survival and migration of murine boundary cap neural crest stem cells (bNCSCs) and embryonic stem cells (ESCs)-derived, predifferentiated neuron precursors after their implantation acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord. Both types of cells survived transplantation, but showed distinctly different modes of migration. Thus, bNCSCs migrated into the spinal cord, expressed glial markers and formed elongated tubes in the peripheral nervous system (PNS) compartment of the avulsed dorsal root transitional zone (DRTZ) area. In contrast, the ESC transplants remained at the site of implantation and differentiated to motor neurons and interneurons. These data show that both stem cell types successfully survived implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. These data suggest that, depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Department of Neuroscience, Regenerative Neurobiology, Uppsala University, Sweden.
authors.forename: Niclas
authors.initials: N
authors.lastname: Konig
authors.affiliation: Department of Neuroscience, Regenerative Neurobiology, Uppsala University, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Trolle
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb School of Medicine, Croatia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kapuralin
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Igor
authors.initials: I
authors.lastname: Adameyko
authors.affiliation: Croatian Institute for Brain Research, University of Zagreb School of Medicine, Croatia.
authors.forename: Dinko
authors.initials: D
authors.lastname: Mitrecic
authors.affiliation: Department of Neuroscience, Regenerative Neurobiology, Uppsala University, Sweden.
authors.forename: Hakan
authors.initials: H
authors.lastname: Aldskogius
authors.affiliation: Centre for Neuroscience and Trauma, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Shortland
authors.affiliation: Department of Neuroscience, Regenerative Neurobiology, Uppsala University, Sweden.
authors.forename: Elena N
authors.initials: EN
authors.lastname: Kozlova
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D002470:Cell Survival; D017690:Cell Transplantation; D053595:Embryonic Stem Cells / Q000166:cytology*; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000502:physiology; D009432:Neural Crest / Q000166:cytology*; D058953:Neural Stem Cells / Q000166:cytology; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013126:Spinal Nerve Roots / Q000473:pathology*
keywords: Schwann cells; dorsal root transitional zone; glial cells; migration; motor neurons; regeneration; sensory neuron; spinal cord