Exp Mol Med.  2008 Feb;40(1):84-91. 10.3858/emm.2008.40.1.84.

Migration of human neural stem cells toward an intracranial glioma

Affiliations
  • 1Neuroscience Graduate Program, Ajou University School of Medicine,Suwon 443-721, Korea. lma52347@ajou.ac.kr
  • 2Brain Disease Research Center, Ajou University School of Medicine, Suwon 443-721, Korea.
  • 3Korea Nanobiotechnology Center, Pusan National University, Busan 609-735, Korea.phkay@pusan.ac.kr

Abstract

Many in vivo and in vitro studies have demonstrated the targeted migration of neural stem cells (NSC) to infiltrating brain tumors, including malignant glioma, highlighting a potential therapeutic approach. However, there is not enough information to apply this approach to clinical therapy. The most important things in stem cell therapy for brain tumors involve selecting the appropriate neural progenitor type and optimizing the efficiency of the cell engraftment. By histological analysis using two different live-dyes, human NSCs were shown to migrate away from the transplanted site in the direction of the expanding C6 glioma and to intermix with the tumor bed, especially with the tumor core. This intermixing occurred within 7 days when NSCs were implanted into glioma model. The time course of migratory HB1.F5 with the greatest mobility of three NSC lines was as follows. As early as 3 days after transplantation, several NSCs were found leaving the implant site, primarily approaching microsatellites and frontier cells located near the site of NSC implantation. Through 7 days post-transplantation, massive numbers of NSCs continued to be attracted to and interspersed with C6 glioma, and were finally distributed extensively throughout the whole tumor bed, including the core and penumbra of the tumor mass. However, NSCs appeared to penetrate into the tumor mass very well, whereas normal fibroblast cells could not migrate. These findings strengthen the potential for human NSCs as attractive vehicles to improve therapeutic gene delivery to cancer or glioma if they are optimized to selectively kill neoplastic cells.

Keyword

glioma; stem cells; tissue therapy; tropism

MeSH Terms

Animals
Brain/*cytology/*pathology
Brain Neoplasms/*pathology
*Cell Movement
Female
Glioma/*pathology
Humans
Mice
NIH 3T3 Cells
Neurons/*cytology
Rats
Rats, Sprague-Dawley
Stem Cells/*cytology
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