Neural Stem Cell Applications in Glioma Therapy

Glioma, particularly glioblastoma, presents formidable challenges due to its infiltrative growth, resistance to conventional treatments and the protective blood–brain barrier that limits drug delivery. Neural stem cells (NSCs) have emerged as a versatile platform for targeted therapy owing to their innate tumour tropism—the capacity to home in on invasive tumour cells and traverse normal brain parenchyma. Engineered NSCs can be designed to deliver a spectrum of therapeutic agents directly to tumour foci, encompassing prodrug-activating enzymes that convert inert compounds into cytotoxic agents, tumouricidal cytokines, oncolytic viruses and monoclonal antibodies. Advances in cellular reprogramming have enabled the generation of induced NSCs (iNSCs) from somatic cells, facilitating autologous treatments that minimise immunogenicity. NSC-based therapies have been administered via intracerebral, intraventricular and non-invasive intranasal routes, with delivery methods such as Ommaya reservoirs allowing repeated dosing. Combined cell therapy platforms, including co-administration with chimeric antigen receptor (CAR)-T cells, have demonstrated synergistic effects, enhancing immune infiltration and antitumour efficacy. Preclinical and early clinical studies highlight the potential of NSC approaches to improve tumour coverage, reduce off-target toxicity and prolong survival in glioma models, paving the way for next-generation personalised therapies.

Research from Nature Portfolio

Therapeutically engineered induced neural stem cells transdifferentiated from somatic cells retain multipotency and intrinsic tumour tropism, selectively migrating to patient-derived glioblastoma xenografts in murine models. These iNSCs have been genetically modified to express tumour necrosis-related apoptosis-inducing ligand, delivering a potent apoptotic stimulus that reduces tumour burden several-fold and extends median survival. Time-lapse and multimodal imaging confirm extensive migration of iNSCs to diffuse tumour foci, demonstrating sustained viability and therapeutic gene expression in the hostile tumour microenvironment. This work establishes a robust framework for autologous cell-based therapy, combining the advantages of direct tumour targeting with controlled delivery of anticancer agents.

Neural Stem Cell Applications in Glioma Therapy publication trend

The graph below shows the total number of articles in neural stem cell applications in glioma therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Neural stem cells (NSCs): Multipotent progenitors capable of self-renewal and differentiation into neurons, astrocytes and oligodendrocytes, harnessed for targeted therapy due to innate tumour tropism.

Induced neural stem cells (iNSCs): NSC-like cells generated via direct transdifferentiation of somatic cells, offering an autologous source for personalised treatment.

Tumour tropism: The inherent migratory capacity of certain cells to home in on and infiltrate tumour microenvironments.

Chimeric antigen receptor (CAR)-T cells: Genetically engineered T lymphocytes expressing synthetic receptors that target specific tumour antigens.

Oncolytic virus: A replication-competent virus engineered to selectively infect and kill cancer cells while stimulating antitumour immunity.

Prodrug-activating enzymes: Enzymes delivered by NSCs that convert systemically administered inert compounds into active cytotoxic drugs at the tumour site.

Ommaya reservoir: An implanted device enabling repeated intracerebral or intraventricular infusions directly into the central nervous system.

References

1. Utilizing induced neural stem cell‐based delivery of a cytokine cocktail to enhance chimeric antigen receptor‐modified T‐cell therapy for brain cancer. Bioengineering & Translational Medicine (2023).
2. Therapeutically engineered induced neural stem cells are tumour-homing and inhibit progression of glioblastoma. Nature Communications (2016).
3. Pharmacologic modulation of nasal epithelium augments neural stem cell targeting of glioblastoma. Theranostics (2019).
4. Quantitative Evaluation of Intraventricular Delivery of Therapeutic Neural Stem Cells to Orthotopic Glioma. Frontiers in Oncology (2019).
5. Human Neural Stem Cell Biodistribution and Predicted Tumor Coverage by a Diffusible Therapeutic in a Mouse Glioma Model. Stem Cells Translational Medicine (2017).
6. Neural Stem Cells as a Novel Platform for Tumor-Specific Delivery of Therapeutic Antibodies. PLOS ONE (2009).