# Nanofiber matrices to improve neural stem cell-mediated cancer therapy

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $330,099

## Abstract

Project Summary/Abstract
Genetically engineered tumoricidal neural stem cells (tNSCs) are a promising therapy for
the highly aggressive brain cancer Glioblastoma (GBM). Engineered tNSCs have unique
tumor-homing capacity that allows them to deliver anti-cancer gene products directly into
local and invasive GBM foci. We recently discovered that polymeric scaffolds
significantly increase the survival of therapeutic stem cells in the GBM resection cavity,
remained permissive to stem cell tumoritropic homing, and markedly prolong the survival
of mice with post-operative GBM. Yet, limitations to scaffold design are likely to prevent
the effective application of scaffold/tNSC therapy in a clinical setting. Additionally, the
matrix properties that regulate tNSC therapy are unknown, preventing the optimization of
scaffold parameters in order to develop a scaffold/tNSC treatment that is effective
against post-surgical GBM in patients. Our results show that altering fiber diameter and
gelatin doping within scaffolds improves tNSC transplant. This allows us to hypothesize
that optimizing the design features of scaffolds will achieve effective suppression of post-
surgical GBMs by tNSC therapy. We propose to identify the scaffold features that
promote tNSC cancer therapy by using a panel of scaffolds with different biophysical and
biochemical features known to influence stem cell adherence, movement, and
differentiation. We will then determine the ability of scaffolds incorporating multiple
optimized features to improve tNSC therapy using surgical resection models of patient-
derived human xenografts in immune-depleted mice and syngeneic GBM allografts in
immune-competent animals. We propose to undertake the following Aims: 1) Develop
and characterize a panel of polymeric scaffolds with differing topographic, mechanical,
and biochemical properties; 2) Determine the scaffold design parameters that regulate
tNSC therapy for post-operative GBM; 3) Investigate the efficacy and safety of
tumoricidal tSC therapy in immune-competent models of GBM resection/recurrence. The
results of our study will generate a therapeutic tNSC/scaffold transplant strategy capable
of robust GBM killing that can be translated for human patient testing. It will also uncover
the scaffold features that regulate different aspects of tNSCs, allowing us to modulate
tNSC cancer therapy through matrix design.

## Key facts

- **NIH application ID:** 9934289
- **Project number:** 5R01NS097507-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Shawn Hingtgen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $330,099
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934289

## Citation

> US National Institutes of Health, RePORTER application 9934289, Nanofiber matrices to improve neural stem cell-mediated cancer therapy (5R01NS097507-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934289. Licensed CC0.

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