Transplantation of neural stem/progenitor cells at different locations in mice with spinal cord injury

Hiroki Iwai, Satoshi Nori, Soraya Nishimura, Akimasa Yasuda, Morito Takano, Osahiko Tsuji, Kanehiro Fujiyoshi, Yoshiaki Toyama, Hideyuki Okano, Masaya Nakamura

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Transplantation of neural stem/progenitor cells (NS/PCs) promotes functional recovery after spinal cord injury (SCI); however, few studies have examined the optimal site of NS/PC transplantation in the spinal cord. The purpose of this study was to determine the optimal transplantation site of NS/PCs for the treatment of SCI. Wild-type mice were generated with contusive SCI at the T10 level, and NS/PCs were derived from fetal transgenic mice. These NS/PCs ubiquitously expressed ffLuc-cp156 protein (Venus and luciferase fusion protein) and so could be detected by in vivo bioluminescence imaging 9 days postinjury. NS/PCs (low: 250,000 cells per mouse; high: 1 million cells per mouse) were grafted into the spinal cord at the lesion epicenter (E) or at rostral and caudal (RC) sites. Phosphate-buffered saline was injected into E as a control. Motor functional recovery was better in each of the transplantation groups (E-Low, E-High, RC-Low, and RC-High) than in the control group. The photon counts of the grafted NS/PCs were similar in each of the four transplantation groups, suggesting that the survival of NS/PCs was fairly uniform when more than a certain threshold number of cells were transplanted. Quantitative RT-PCR analyses demonstrated that brain-derived neurotropic factor expression was higher in the RC segment than in the E segment, and this may underlie why NS/PCs more readily differentiated into neurons than into astrocytes in the RC group. The location of the transplantation site did not affect the area of spared fibers, angiogenesis, or the expression of any other mediators. These findings indicated that the microenvironments of the E and RC sites are able to support NS/PCs transplanted during the subacute phase of SCI similarly. Optimally, a certain threshold number of NS/PCs should be grafted into the E segment to avoid damaging sites adjacent to the lesion during the injection procedure.

Original languageEnglish
Pages (from-to)1415-1464
Number of pages50
JournalCell Transplantation
Volume23
Issue number11
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • Cell transplantation
  • Neural stem/progenitor cells (NS/PCs)
  • Spinal cord injury (SCI)
  • Subacute phase
  • Transplantation site

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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