Skip to main content

Malignant Gliomas: Treatment Using Genetically-Modified Neural Stem Cells

  • Chapter
  • First Online:
Book cover Stem Cells and Cancer Stem Cells, Volume 4

Part of the book series: Stem Cells and Cancer Stem Cells ((STEM,volume 4))

  • 1122 Accesses

Abstract

Glioblastoma multiforme (GBM), the most aggressive form of primary brain tumors, contain small population of tumor cells that carry cancer stem cell properties. These brain tumor stem cells (BTSCs) are highly invasive and mobile, have the capacity to self-renew, and are more resistant to radiation and chemotherapy. BTSCs can migrate away from the primary tumor sites and form microsatellite tumors. Thus, BTSCs have been proposed to play a key role in tumor progression, metastasis, and recurrence. Recent studies indicate that neural stem cells have the innate ability to track down tumor cells and may even slow tumor growth and progression. Thus, therapeutic neural stem cells can be developed by “arming” normal neural stem cells with genes cytotoxic to glioma cells and, more importantly, to BTSCs. Studies are currently underway to explore this new therapeutic approach to treat GBM using neural stem cells.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

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

    Article  PubMed  CAS  Google Scholar 

  • Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, Dewhirst MW, Bigner DD, Rich JN (2006a) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760

    Article  PubMed  CAS  Google Scholar 

  • Bao S, Wu Q, Sathornsumetee S, Hao Y, Li Z, Hjelmeland AB, Shi Q, McLendon RE, Bigner DD, Rich JN (2006b) Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 66:7843–7848

    Article  PubMed  CAS  Google Scholar 

  • Barresi V, Belluardo N, Sipione S, Mudo G, Cattaneo E, Condorelli DF (2003) Transplantation of prodrug-converting neural progenitor cells for brain tumor therapy. Cancer Gene Ther 10:396–402

    Article  PubMed  CAS  Google Scholar 

  • Benedetti S, Pirola B, Pollo B, Magrassi L, Bruzzone MG, Rigamonti D, Galli R, Selleri S, Di Meco F, De Fraja C et al (2000) Gene therapy of experimental brain tumors using neural progenitor cells. Nat Med 6:447–450

    Article  PubMed  CAS  Google Scholar 

  • Blazek ER, Foutch JL, Maki G (2007) Daoy medulloblastoma cells that express CD133 are radioresistant relative to CD133- cells, and the CD133+ sector is enlarged by hypoxia. Int J Radiat Oncol Biol Phys 67:1–5

    Article  PubMed  CAS  Google Scholar 

  • Brunda MJ (1994) Interleukin-12. J Leukoc Biol 55:280–288

    PubMed  CAS  Google Scholar 

  • Demuth T, Berens ME (2004) Molecular mechanisms of glioma cell migration and invasion. J Neurooncol 70:217–228

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Ehtesham M, Yuan X, Kabos P, Chung NH, Liu G, Akasaki Y, Black KL, Yu JS (2004) Glioma tropic neural stem cells consist of astrocytic precursors and their migratory capacity is mediated by CXCR4. Neoplasia 6:287–293

    Article  PubMed  CAS  Google Scholar 

  • Fan X, Khaki L, Zhu TS, Soules ME, Talsma CE, Gul N, Koh C, Zhang J, Li YM, Maciaczyk J et al (2010) NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells 28:5–16

    PubMed  CAS  Google Scholar 

  • Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S, Fiocco R, Foroni C, Dimeco F, Vescovi A (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma. Cancer Res 64:7011–7021

    Article  PubMed  CAS  Google Scholar 

  • Giese A, Bjerkvig R, Berens ME, Westphal M (2003) Cost of migration: invasion of malignant gliomas and implications for treatment. J Clin Oncol 21:1624–1636

    Article  PubMed  CAS  Google Scholar 

  • Glass R, Synowitz M, Kronenberg G, Walzlein JH, Markovic DS, Wang LP, Gast D, Kiwit J, Kempermann G, Kettenmann H (2005) Glioblastoma-induced attraction of endogenous neural precursor cells is associated with improved survival. J Neurosci 25:2637–2646

    Article  PubMed  CAS  Google Scholar 

  • Jeong M, Kwon YS, Park SH, Kim CY, Jeun SS, Song KW, Ko Y, Robbins PD, Billiar TR, Kim BM, Seol DW (2009) Possible novel therapy for malignant gliomas with secretable trimeric TRAIL. PLoS One 4:e4545

    Article  PubMed  Google Scholar 

  • Kikuchi T, Joki T, Saitoh S, Hata Y, Abe T, Kato N, Kobayashi A, Miyazaki T, Ohno T (1999) Anti-tumor activity of interleukin-2-producing tumor cells and recombinant interleukin 12 against mouse glioma cells located in the central nervous system. Int J Cancer 80:425–430

    Article  PubMed  CAS  Google Scholar 

  • Kim CY, Jeong M, Mushiake H, Kim BM, Kim WB, Ko JP, Kim MH, Kim M, Kim TH, Robbins PD et al (2006) Cancer gene therapy using a novel secretable trimeric TRAIL. Gene Ther 13:330–338

    Article  PubMed  CAS  Google Scholar 

  • Kim JH, Lee JE, Kim SU, Cho KG (2010) Stereological analysis on migration of human neural stem cells in the brain of rats bearing glioma. Neurosurgery 66:333–342; discussion 342

    Article  PubMed  Google Scholar 

  • Kim SK, Cargioli TG, Machluf M, Yang W, Sun Y, Al-Hashem R, Kim SU, Black PM, Carroll RS (2005) PEX-producing human neural stem cells inhibit tumor growth in a mouse glioma model. Clin Cancer Res 11:5965–5970

    Article  PubMed  CAS  Google Scholar 

  • Kim SM, Lim JY, Park SI, Jeong CH, Oh JH, Jeong M, Oh W, Park SH, Sung YC, Jeun SS (2008) Gene therapy using TRAIL-secreting human umbilical cord blood-derived mesenchymal stem cells against intracranial glioma. Cancer Res 68:9614–9623

    Article  PubMed  CAS  Google Scholar 

  • Lefranc F, Brotchi J, Kiss R (2005) Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis. J Clin Oncol 23:2411–2422

    Article  PubMed  CAS  Google Scholar 

  • Li S, Tokuyama T, Yamamoto J, Koide M, Yokota N, Namba H (2005a) Bystander effect-mediated gene therapy of gliomas using genetically engineered neural stem cells. Cancer Gene Ther 12:600–607

    Article  PubMed  CAS  Google Scholar 

  • Li S, Tokuyama T, Yamamoto J, Koide M, Yokota N, Namba H (2005b) Potent bystander effect in suicide gene therapy using neural stem cells transduced with herpes simplex virus thymidine kinase gene. Oncology 69:503–508

    Article  PubMed  Google Scholar 

  • Li Z, Bao S, Wu Q, Wang H, Eyler C, Sathornsumetee S, Shi Q, Cao Y, Lathia J, McLendon RE et al (2009) Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell 15:501–513

    Article  PubMed  CAS  Google Scholar 

  • Liu G, Yuan X, Zeng Z, Tunici P, Ng H, Abdulkadir IR, Lu L, Irvin D, Black KL, Yu JS (2006) Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5:67

    Article  PubMed  Google Scholar 

  • Lukas RV, Boire A, Nicholas MK (2009) Targeted therapy in the treatment of malignant gliomas. Onco Targets Ther 2:115–133

    PubMed  CAS  Google Scholar 

  • Pluderi M, Lucini V, Caronzolo D, Pannacci M, Costa F, Carrabba G, Giussani C, Grosso S, Colleoni F, Scaglione F et al (2003) Long-term inhibition of glioma growth by systemic administration of human PEX. J Neurosurg Sci 47:69–78

    PubMed  CAS  Google Scholar 

  • Rainov NG (2000) A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Hum Gene Ther 11:2389–2401

    Article  PubMed  CAS  Google Scholar 

  • Singh SK, Clarke ID, Hide T, Dirks PB (2004) Cancer stem cells in nervous system tumors. Oncogene 23:7267–7273

    Article  PubMed  CAS  Google Scholar 

  • Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466

    Article  PubMed  CAS  Google Scholar 

  • Tada M, de Tribolet N (1993) Recent advances in immunobiology of brain tumors. J Neurooncol 17:261–271

    Article  PubMed  CAS  Google Scholar 

  • Trounson A (2009) New perspectives in human stem cell therapeutic research. BMC Med 7:29

    Article  PubMed  Google Scholar 

  • Tsurushima H, Yuan X, Dillehay LE, Leong KW (2007) Radioresponsive tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene therapy for malignant brain tumors. Cancer Gene Ther 14:706–716

    Article  PubMed  CAS  Google Scholar 

  • van Eekelen M, Sasportas LS, Kasmieh R, Yip S, Figueiredo JL, Louis DN, Weissleder R, Shah K (2010) Human stem cells expressing novel TSP-1 variant have anti-angiogenic effect on brain tumors. Oncogene 29:3185–3195

    Article  PubMed  Google Scholar 

  • Wang J, Wakeman TP, Lathia JD, Hjelmeland AB, Wang XF, White RR, Rich JN, Sullenger BA (2010) Notch promotes radioresistance of glioma stem cells. Stem Cells (Dayton, Ohio) 28:17–28

    Article  CAS  Google Scholar 

  • Yang SY, Liu H, Zhang JN (2004) Gene therapy of rat malignant gliomas using neural stem cells expressing IL-12. DNA Cell Biol 23:381–389

    Article  PubMed  CAS  Google Scholar 

  • Yuan X, Hu J, Belladonna ML, Black KL, Yu JS (2006) Interleukin-23-expressing bone marrow-derived neural stem-like cells exhibit antitumor activity against intracranial glioma. Cancer Res 66:2630–2638

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael C. Oh .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Oh, M.C., Berger, M.S., Lim, D.A. (2012). Malignant Gliomas: Treatment Using Genetically-Modified Neural Stem Cells. In: Hayat, M. (eds) Stem Cells and Cancer Stem Cells, Volume 4. Stem Cells and Cancer Stem Cells, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2828-8_20

Download citation

Publish with us

Policies and ethics