Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Fujimoto, Yusuke ; Abematsu, Masahiko ; Falk, Anna LU ; Tsujimura, Keita ; Sanosaka, Tsukasa ; Juliandi, Berry ; Semi, Katsunori ; Namihira, Masakazu ; Komiya, Setsuro and Smith, Austin , et al. (2012) In Stem Cells 30(6). p.73-1163
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; and (Less)
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Cell Differentiation/physiology, Cells, Cultured, Disease Models, Animal, Female, Humans, Immunohistochemistry, Induced Pluripotent Stem Cells/cytology, Mice, Mice, Inbred NOD, Mice, SCID, Neural Stem Cells/metabolism, Spinal Cord Injuries/pathology, Stem Cell Transplantation/methods
in
Stem Cells
volume
30
issue
6
pages
11 pages
publisher
Oxford University Press
external identifiers
  • scopus:84861839572
  • pmid:22419556
ISSN
1549-4918
DOI
10.1002/stem.1083
language
English
LU publication?
no
id
7a9de730-629a-442f-885f-b058105ec70f
date added to LUP
2021-08-10 13:38:03
date last changed
2024-04-06 06:44:57
@article{7a9de730-629a-442f-885f-b058105ec70f,
  abstract     = {{<p>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.</p>}},
  author       = {{Fujimoto, Yusuke and Abematsu, Masahiko and Falk, Anna and Tsujimura, Keita and Sanosaka, Tsukasa and Juliandi, Berry and Semi, Katsunori and Namihira, Masakazu and Komiya, Setsuro and Smith, Austin and Nakashima, Kinichi}},
  issn         = {{1549-4918}},
  keywords     = {{Animals; Cell Differentiation/physiology; Cells, Cultured; Disease Models, Animal; Female; Humans; Immunohistochemistry; Induced Pluripotent Stem Cells/cytology; Mice; Mice, Inbred NOD; Mice, SCID; Neural Stem Cells/metabolism; Spinal Cord Injuries/pathology; Stem Cell Transplantation/methods}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{73--1163}},
  publisher    = {{Oxford University Press}},
  series       = {{Stem Cells}},
  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}},
  url          = {{https://lup.lub.lu.se/search/files/101077089/Treatment_of_a_mouse_model.pdf}},
  doi          = {{10.1002/stem.1083}},
  volume       = {{30}},
  year         = {{2012}},
}