title: Treatment of a mouse model of spinal cord injury by transplantation of human induced pluripotent stem cell-derived long-term self-renewing neuroepithelial-like stem cells.
abstract: Because of their ability to self-renew, to differentiate into multiple lineages, and to migrate toward a damaged site, neural stem cells (NSCs), which can be derived from various sources such as fetal tissues and embryonic stem cells, are currently considered to be promising components of cell replacement strategies aimed at treating injuries of the central nervous system, including the spinal cord. Despite their efficiency in promoting functional recovery, these NSCs are not homogeneous and possess variable characteristics depending on their derivation protocols. The advent of induced pluripotent stem (iPS) cells has provided new prospects for regenerative medicine. We used a recently developed robust and stable protocol for the generation of long-term, self-renewing, neuroepithelial-like stem cells from human iPS cells (hiPS-lt-NES cells), which can provide a homogeneous and well-defined population of NSCs for standardized analysis. Here, we show that transplanted hiPS-lt-NES cells differentiate into neural lineages in the mouse model of spinal cord injury (SCI) and promote functional recovery of hind limb motor function. Furthermore, using two different neuronal tracers and ablation of the transplanted cells, we revealed that transplanted hiPS-lt-NES cell-derived neurons, together with the surviving endogenous neurons, contributed to restored motor function. Both types of neurons reconstructed the corticospinal tract by forming synaptic connections and integrating neuronal circuits. Our findings indicate that hiPS-lt-NES transplantation represents a promising avenue for effective cell-based treatment of SCI.
authors.affiliation: Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Fujimoto
authors.forename: Masahiko
authors.initials: M
authors.lastname: Abematsu
authors.forename: Anna
authors.initials: A
authors.lastname: Falk
authors.forename: Keita
authors.initials: K
authors.lastname: Tsujimura
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Sanosaka
authors.forename: Berry
authors.initials: B
authors.lastname: Juliandi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Semi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Namihira
authors.forename: Setsuro
authors.initials: S
authors.lastname: Komiya
authors.forename: Austin
authors.initials: A
authors.lastname: Smith
authors.forename: Kinichi
authors.initials: K
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000637:transplantation*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D058953:Neural Stem Cells / Q000378:metabolism / Q000637:transplantation*; D013119:Spinal Cord Injuries / Q000473:pathology / Q000601:surgery*; D033581:Stem Cell Transplantation / Q000379:methods