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Neural Stem Cells as Therapeutic Delivery Vehicles for Malignant Brain Tumors

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Stem Cells: Current Challenges and New Directions

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Malignant brain tumors are nearly untreatable due to their highly infiltrative nature and resistance to existing therapies. The main reason for recurrent tumor growth is believed to be the presence of tumor cells that migrate great distances into the brain tissue. In addition, poor delivery of therapeutics to the tumors due to blood–brain barrier limits the clinical success of currently available systemically delivered antitumor therapies. Recently, a different mode of therapeutic delivery, whereby therapeutic biomolecules are expressed by tumor-tropic neural stem cells (NSCs), has gained considerable attention. Exploiting the intrinsic tumor-homing ability of NSCs, the past decade has witnessed significant advances in the discovery and development of NSC-based therapies for malignant brain tumors. Prodrug converting enzymes, immunomodulatory cytokines, pro-apoptotic (tumouricidal) agents, growth-inhibiting factors, anti-angiogenic agents, and viral particles have been among the most commonly studied antitherapeutic molecules produced by NSCs. While the mechanisms of tumor-directed NSC migration and fate of NSCs after engrafting are still not truly understood, the results from current preclinical tumor models have demonstrated promising utility for NSCs as “armed vehicles” in treatment of aggressive brain tumors. Indeed, the first clinical trial with NSC-delivered antitumor agents is now in progress for recurrent gliomas.

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Abbreviations

GBM:

Glioblastoma multiforme

TMZ:

Temozolomide

BBB:

Blood–brain barrier

NSC:

Neural stem cell

CNS:

Central nervous system

ES:

Embryonic stem

SVZ:

Subventricular zone

Fluc:

Firefly luciferase

Rluc:

Renilla luciferase

MRI:

Magnetic resonance imaging

BLI:

Bioluminescence imaging

FE-Pro:

Ferumoxide protamine sulfate complex

SF/HGF:

Scatter factor/hepatocyte growth factor

SDF-1:

Stromal-derived factor

CXCR4:

CXC chemokine receptor 4

VEGF:

Vascular endothelial growth factor

PI3K:

Phosphoinositide 3 kinase

TMEM18:

Transmembrane protein 18

ECM:

Extracellular matrix

PCE:

Prodrug converting enzyme

HSV-TK:

Herpes simplex virus-thymidine kinase

CD:

Cytosine deaminase

CE:

Carboxylesterase

GCV:

Ganciclovir

5-FC:

5-Fluorocytosine

5-FU:

5-Fluorouracil

CPT-11:

Camptothecin-11

CPA:

Cyclophosphamide

CYP2B6:

CPA-activating enzyme cytochrome p450 2B6

TSP:

Thrombospondin

OV:

Oncolytic virus

CRAd:

Conditionally replicating adenovirus

MMP:

Matrix metalloproteinase

EGFR:

Epidermal growth factor receptor

ENb:

EGFR targeting nanobody

IL:

Interleukin

IFN:

Interferon

BM-NSC:

Bone marrow-derived NSC

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligand

GMP:

Good manufacturing practice

iPSc:

Induced pluripotent stem cell

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Authors and Affiliations

  1. Koç University School of Medicine, Rumelifeneri Yolu, Sariyer, Istanbul, 34450, Turkey

    Tugba Bagci-Onder

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  1. Tugba Bagci-Onder
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Correspondence to Tugba Bagci-Onder .

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  1. Regenerative Medicine Program, Ottawa Hospital Research Institute Sprott Centre for Stem Cell Research, Ottawa, Ontario, Canada

    Kursad Turksen

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Bagci-Onder, T. (2013). Neural Stem Cells as Therapeutic Delivery Vehicles for Malignant Brain Tumors. In: Turksen, K. (eds) Stem Cells: Current Challenges and New Directions. Stem Cell Biology and Regenerative Medicine. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-8066-2_12

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