[Frontiers in Bioscience S3, 698-708, January 1, 2011]

Cryopreservation of cancer-initiating cells derived from glioblastoma

Charlene Shu Fen Foong1,2, Felicia Soo Lee Ng3, Mark Phong3, Tan Boon Toh2, Yuk Kien Chong1,2, Greg Tucker-Kellogg3,4, Robert Morris Campbell3, Beng Ti Ang1,2,5,6, Carol Tang5,7

1Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Brenner Centre for Molecular Science, 30 Medical Drive, Singapore 117609, 2Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9, 2 Medical Drive, Singapore 117597, 3Lilly Singapore Centre for Drug Discovery (Eli Lilly and Company), 8A Biomedical Grove, #02-05 Immunos, Singapore 138648, 4Department of Biological Sciences, Faculty of Science, National University of Singapore, 14 Science Drive 4, Singapore 117543, 5Duke-NUS Graduate Medical School, 8 College Road, Singapore 169857, Departments of 6Neurosurgery and 7Research, National Neuroscience Institute, 11, Jalan Tan Tock Seng, Singapore 308433

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Vitrification: A cryopreservation technique for GBM-initiating cells
3.1. Preservation of essential properties
3.2. Model for maintenance of GBM-initiating cells
4. GBM-initiating cell subtypes and their relation to published cell collections
5. Application: Drug screening and common oncologic pathways
6. Summary
7. Acknowledgements
8. References

1. ABSTRACT

Glioblastoma multiforme (GBM) represents the most devastating adult brain tumor. GBM follows a hierarchical development in oncogenesis, with a sub-population of cells - brain tumor stem cells (BTSCs), exhibiting tumor-initiating potential. BTSCs possess extensive self-renewal capability and can repopulate the entire tumor mass. They are resistant to conventional therapies, suggesting that they are the likely candidates of tumor recurrence. Their eradication is thus important for an effective cure. Previous works showed that human-derived BTSCs could be stably maintained for 10-15 passages in serum-free condition, and gene expression and karyotypic hallmarks similar to the primary tumors were preserved. However, primary cells have been shown to sustain additional karyotypic aberrations owing to the harsh conditions of extended in vitro serial passage. Several investigators have proposed passaging these cells in xenograft models. A limitation of such an approach is the inability to return to identical passages for experimental repetitions, or the unavailability of suitably-aged mice for implantation. We have devised a method to cryopreserve BTSCs and that important characteristics were maintained, establishing a repository for drug screening endeavors.