Stereological analysis on migration of human neural stem cells in the brain of rats bearing glioma.

Objective: The objective of this study was to determine the rate and pattern of NSC migration in the brain and its time course after NSC transplantation.

Methods: We investigated the tropism of HB1.F3 (F3) immortalized human NSCs in rats bearing U373 human glioma in the brain. Rats received an injection of human U373MG malignant glioma cells into the striatum followed by an injection of F3 cells into the contralateral hemisphere 7 days later. We analyzed the numbers, distribution, and migration rate of NSCs using unbiased stereology.

Results: Approximately 10% of the injected NSCs migrated into the tumor region by 50 minutes after NSC injection. The number of NSCs in the tumor region increased slowly up to 5 days post-injection and increased significantly up to 15 days post-injection. Changes in tumor volume showed similar patterns. The rate of NSC migration was approximately 175 microm/min. NSCs increased in number approximately 1.7-fold during day 1 in the absence of tumor cell inoculation in vivo. However, the proliferation of NSCs began to decline after 5 days after injection.

Conclusion: We identified for the first time the rate and pattern of NSC migration to the tumor mass in vivo. These findings may provide useful information with respect to preclinical research of gene therapy for malignant gliomas.