Skip to main content

Maintaining and Engineering Neural Stem Cells for Delivery of Genetically Encoded Therapy to Brain Tumors

  • Protocol
  • First Online:
Cancer Stem Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 568))

  • 2313 Accesses

Summary

Despite advances for the treatment of cancer, the prognosis for patients suffering from malignant brain tumors remains dismal. High-grade neoplasms, such as gliomas, are highly invasive and spawn widely disseminated microsatellites that have limited the efficacy of surgical and adjunctive therapies. The cancer stem cell hypothesis suggests that conventional chemotherapeutic treatments kill differentiated and differentiating cells which often form the bulk of the tumor. One major concern is that the cells which give rise to the tumor, the cancer stem cells, remain untouched and may be responsible for a relapse of the disease. Therefore, an adjunctive therapy to current cancer treatment is critical for the survivability of patients suffering from brain tumors. We have successfully engineered tumor-tropic neural stem cells to deliver antineoplastic gene products directly to the tumor-producing cells. This potential therapeutic strategy may safely eradicate tumor-producing cells in the brain while minimizing damage to normal, healthy cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Snyder, EY., Deichter, DL., Walsh, C., Arnold-Aldea, S., Hartweig, EA., and Cepko, CL. Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell, 68: 33–51, 1992.

    Article  PubMed  CAS  Google Scholar 

  2. Yip, S., Aboody, KS., Burns, M., Imitola, J., Boockvar, JA., Allport, J., Park, KI., Teng, YD., Lachyankar, M., McIntosh, T., O’Rourke, DM., Khoury, S., Weissleder, R., Black, PM., Weiss, W., and Snyder, EY. Neural stem cell biology may be well suited for improving brain tumor therapies. Cancer J., 9: 189–204, 2003.

    Article  PubMed  CAS  Google Scholar 

  3. Aboody, KS., Brown, A., Rainov, NG., Bower, KA., Liu, S., Yang, W., Small, JE., Herrlinger, U., Ourednik, V., Black, PM., Breakefield, XO., and Snyder, EY. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc. Natl. Acad. Sci. USA., 97: 12846–12851, 2000.

    Article  PubMed  CAS  Google Scholar 

  4. Elzaouk, L., Moelling, K., and Pavlovic, J. Anti-tumor activity of mesenchymal stem cells producing IL-12 in a mouse melanoma model. Exp. Dermatology, 15: 865–874, 2006.

    Article  CAS  Google Scholar 

  5. Song, K., Benhaga N., Anderson, RL., and Khosravi-Far, R. Transduction of tumor-necrosis factor-related apoptosis-inducing ligand into hematopoietic cells leads to inhibition of syngeneic tumor growth in vivo. Cancer Res., 66(12): 6304–6311, 2006.

    Article  PubMed  CAS  Google Scholar 

  6. Kim, SK., Kim, SU., Park, IH., Bang, JH., Aboody, KS., Wang, KC., Cho, BK., Kim, M., Menon, LG., Black, PM., and Carroll, RS. Human neural stem cells target experimental intracranial medulloblastoma and deliver a therapeutic gene leading to tumor regression. Clin Cancer Res., 12(18): 5550–5556, 2006.

    Article  PubMed  CAS  Google Scholar 

  7. Aboody, KS., Najbauer, J., Schmidt, NO., Yang, W., Wu, JK., Zhuge, Y., Przylecki, W., Carroll, R., Black, PM., and Perides, G. Targeting of melanoma brain metastases using engineered neural stem/progenitor cells. Neuro-Oncol., 8(2): 119–126, 2005.

    Article  Google Scholar 

  8. Ehtesham, M., Kabos, P., Kabosova, A., Neuman, T., Black, KL., and Yu, JS. The use of interleukin 12-secreting neural stem cells for the treatment of intracranial glioma. Cancer Res., 62(20): 5657–5663, 2002.

    PubMed  CAS  Google Scholar 

  9. Yang, YS., Hiu, L. and Zhang, JN. Gene therapy of rat malignant gliomas using neural stem cells expressing IL-12. DNA Cell Biol., 23(6): 381–389, 2004.

    Article  PubMed  CAS  Google Scholar 

  10. Ehtesham, M., Kabos, P., Guitierrez, MA., Chung, NH., Griffith, TS., Black, KL., and Yu, JS. Induction of glioblastoma apoptosis using neural stem cell-mediated delivery of tumor necrosis factor-related apoptosis-inducing ligand. Cancer Res., 62(24): 7170–7174, 2002.

    PubMed  CAS  Google Scholar 

  11. Logan, AC., Haas, DL., Kafri, T., and Kohn, DB. Integrated self-inactivating lentiviral vectors produce full-length genomic transcripts competent for encapsidation and integration. J. Virol., 78: 8421–8436, 2004.

    Article  PubMed  CAS  Google Scholar 

  12. Logan, AC., Nightingale, SJ., Haas, DL., Cho, GJ., Pepper, KA., and Kohn, DB. Factors influencing the titer and infectivity of lentiviral vectors. Hum. Gene Ther., 15: 976–988, 2004.

    Article  PubMed  CAS  Google Scholar 

  13. Miyoshi, H., Smith, KA., Mosier, DE., Verma, IM., and Torbett, BE. Transduction of human CD34+ cells that mediate long-term engraftment of NOD/SCID mice by HIV vectors. Science, 283: 682–686, 1999.

    Article  PubMed  CAS  Google Scholar 

  14. Logan, AC., Lutzko, C., and Kohn, DB. Advances in lentiviral vector design for gene-modification of hematopoietic stem cells. Curr. Opin. Biotechnol., 13: 429–436, 2002.

    Article  PubMed  CAS  Google Scholar 

  15. Van Damme, A., Thorrez, L., Ma, L., Vandenburgh, H., Eyckmans, J., Dell’Accio, F., De Bari, C., Luyten, F., Lillicrap, D., Collen, D., VandenDriessche, T., and Chuah, MK. Efficient lentiviral transduction and improved engraftment of human bone marrow mesenchymal cells. Stem Cells, 24: 896–907, 2006.

    Article  PubMed  Google Scholar 

  16. Schorpp, M., Jager, R., Schellander, K., Schenkel, J., Wagner, EF., Weiher, H., and Angel, P. The human ubiquitin C promoter directs high ubiquitous expression of transgenes in mice. Nucleic Acids Res., 24: 1787–1788, 1996.

    Article  PubMed  CAS  Google Scholar 

  17. Torbett, BE. Reporter genes: too much of a good thing? J. Gene Med., 4: 478–479, 2002.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a Susan G. Komen Breast Cancer Foundation grant PDF0403205 and a CBCRP grant12IB-0122 to B. Felding-Habermann in consortium with EY Snyder.

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Katz, J., Krueger, J., Felding-Habermann, B., Snyder, E.Y. (2009). Maintaining and Engineering Neural Stem Cells for Delivery of Genetically Encoded Therapy to Brain Tumors. In: Yu, J. (eds) Cancer Stem Cells. Methods in Molecular Biology, vol 568. Humana Press. https://doi.org/10.1007/978-1-59745-280-9_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-280-9_16

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-938-3

  • Online ISBN: 978-1-59745-280-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics