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

Yusuke Fujimoto, Masahiko Abematsu, Anna Falk, Keita Tsujimura, Tsukasa Sanosaka, Berry Juliandi, Katsunori Semi, Masakazu Namihira, Setsuro Komiya, Austin Smith, Kinichi Nakashima

研究成果: Contribution to journalArticle査読

170 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1163-1173
ページ数11
ジャーナルSTEM CELLS
30
6
DOI
出版ステータス出版済み - 6 2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 分子医療
  • 発生生物学
  • 細胞生物学

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