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

Source: Cell Transplantation, Volume 20, Number 5, 2011 , pp. 727-739(13)

Publisher: Cognizant Communication Corporation

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 bioluminescence 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.

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

Document Type: Research article

DOI: http://dx.doi.org/10.3727/096368910X536554

Publication date: 2011-05-01

More about this publication?

• Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
  

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• In this Subject: Anatomy & Physiology ,  Biology ,  Biotechnology ,  Pharmacology ,  Surgery
• By this author: Takahashi, Yuichiro ;  Tsuji, Osahiko ;  Kumagai, Gentaro ;  Hara, Chikako Miyauchi ;  Okano, Hirotaka James ;  Miyawaki, Atsushi ;  Toyama, Yoshiaki ;  Okano, Hideyuki ;  Nakamura, Masaya

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