Intranasal delivery of stem cell-based therapies for the treatment of brain malignancies

ABSTRACT

Introduction: Glioblastoma (GBM) is the most aggressive malignant brain cancer in adults, and its poor prognosis and resistance to the existing standard of care require the development of innovative therapeutic modalities. The local delivery of stem cells as therapeutic carriers against glioma has produced encouraging results, but encounters obstacles with regards to the repeatability and invasiveness of administration. Intranasal delivery of therapeutic stem cells could overcome these obstacles, among others, as a noninvasive and easily repeatable mode of administration.

Areas covered: This review describes nasal anatomy, routes of stem cell migration, and factors affecting stem cell delivery to hard-to-reach tumors. Furthermore, this review discusses the molecular mechanisms underlying stem cell migration following delivery, as well as possible stem cell effector functions to be considered in combination with intranasal delivery.

Expert opinion: Further research is necessary to elucidate the dynamics of stem cell effector functions in the context of intranasal delivery and optimize their therapeutic potency. Nonetheless, the technique represents a promising tool against brain cancer and has the potential to be expanded for use against other brain pathologies.

KEYWORDS:

• Glioblastoma
• malignant glioma
• stem cells
• intranasal delivery
• CNS delivery

Article highlights

• Delivery of stem cells through the intranasal route has the potential to overcome many of the challenges of repeated CNS drug delivery currently faced, as it is a non-invasive and easily repeatable technique.

• Differences in nasal anatomy between mouse and human exist and are highlighted.

• Possible routes of migration for stem cells carrying therapeutics are explored, including pathways along the olfactory and trigeminal nerves.

• Both mesenchymal and neural stem cells have a natural tropism towards glioblastoma, which makes them an appealing modality for the delivery of an array of therapeutics for malignant brain tumors.

• Considerations for work that prepares intranasal delivery of stem cell-based therapy into the clinic are investigated.

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Acknowledgements

The authors would like to extend their gratitude to their medical illustrator, Michael Gallagher, for his contribution to this manuscript.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was funded by the U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute, R01CA122930 (MSL) and NIH R01NS087990 (MSL, IVB) and K08NS092895 (MD).