Comparative study of methods for administering neural stem/progenitor cells to treat spinal cord injury in mice

Yuichiro Takahashi, Osahiko Tsuji, Gentaro Kumagai, Chikako Miyauchi Hara, Hirotaka James Okano, Atsushi Miyawaki, Yoshiaki Toyama, Hideyuki Okano, Masaya Nakamura

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

To investigate potential cures for spinal cord injury (SCI), several researchers have transplanted neural stem/progenitor cells (NS/PCs) into the injured spinal cord by different procedures, including intralesional (IL), intrathecal (IT), and intravenous (IV) injection. However, there are no reports quantifying or comparing the number of cells successfully transplanted to the lesion site by each procedure in vivo. The purpose of the present study was to determine the optimal method of cell transplantation to the SCI site in terms of grafted cell survival and safety. For this purpose, we developed mouse NS/PCs that expressed a novel Venus-luciferase fusion protein that enabled us to detect a minimum of 1,000 grafted cells in vivo by biolumines-cence imaging (BLI). After inducing contusive SCI at the T10 level in mice, NS/PCs were transplanted into the injured animals three different ways: by IL, IT, or IV injection. Six weeks after the transplantation, BLI analysis showed that in the IL group, the luminescence intensity of the grafted cells had decreased to about 10% of its initial level, and appeared at the site of injury. In the IT group, the luminescence of the grafted cells, which was distributed throughout the entire subarachnoid space immediately after transplantation, was detected at the injured site 1 week later, and by 6 weeks had gradually decreased to about 0.3% of its initial level. In the IV group, no grafted cells were detected at the site of injury, but all of these mice showed luminescence in the bilateral chest, suggesting pulmonary embolism. In addition, one third of these mice died immediately after the IV injection. In terms of grafted cell survival and safety, we conclude that the IL application of NS/PCs is the most effective and feasible method for transplanting NS/PCs into the SCI site.

Original languageEnglish
Pages (from-to)727-739
Number of pages13
JournalCell Transplantation
Volume20
Issue number5
DOIs
Publication statusPublished - 2011 Jul 11

Keywords

  • Bioluminescence imaging (BLI)
  • Neural stem/progenitor cells (NS/PCs)
  • Spinal cord injury (SCI)
  • Transplantation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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