# Development of Neural Stem Cell mediated therapy for repetitive mild TBI.

> **NIH NIH R03** · ROSKAMP INSTITUTE, INC. · 2020 · $80,000

## Abstract

Traumatic brain injury is a recognized risk factor for later development of neurodegenerative disease.
Brain injuries poses a significant financial burden to society as well as a physical and psychiatric burden to
victims and caregivers. The severity of traumatic brain injury (TBI) ranges from mild to severe, with mild traumatic
brain injury/concussion being three times more common than moderate and severe brain injury combined.
Current acute treatment of TBI is limited to controlling intracranial pressure and there is no therapy to reverse
the primary or secondary injuries associated with any severity of TBI. The use of Neural Stem Cells (NSCs) in
treatment of TBI has gain enormous interest over the last decade. Partly because of their good safety record in
the current clinical trials for stroke or cancer, their ability to migrate across the blood brain barrier, and also by
their ability to circumvent one of the major hurdle in treating TBI, which is a selective and targeted delivery to the
injured tissues. Other advantages such of their immunosuppressive properties and their capability of secreting
growth factors that could halt the progression of the secondary insult make them particularly appealing as a
regenerative therapy post TBI. The goal of this application is to use intranasal delivery of a known doses of a
well-characterized, immortalized human allogeneic NSC line (LM-NSC008) to repair the brain tissues damaged
after mild TBI. Intranasal administration of NSCs, when compared with intracranial administration, appears to be
the least invasive and most feasible and cost-effective option for delivering cells to the brain for repeated
treatment rounds with a focus on patients experiencing long term symptoms (15% of all mTBI). We will determine
the doses and therapeutic efficacy of five intranasal injection of LM-NSC008 cells in our experimental mouse
model of mild TBI. Ex vivo 2-photon confocal microscopy of brain sections and CLARITY will be used to
reconstruct brains three-dimensionally and to quantify the TBI sites coverage by NSCs at 17 days post last injury.
This proposal will also evaluate NSCs survival, engraftment, and associated functional outcome at 2 months
post repetitive mild TBI. We hypothesize that the ongoing inflammation observed in the white matter of the
injured animals of our experimental model of mTBI could be alleviated by multiple intranasal injections of NSCs
and improve functional recovery. Because LM-NSC008 cells has been shown to migrate through the sub cortical
white matter tracts, we anticipate to see, a decrease in reactive gliois in the major white matter tracts concurrent
with a decrease in proinflammatory cytokines that correlates with an amelioration of injury-induced cognitive
deficits. Successful translation of this approach would be a major advance over current methods of stem cell
delivery to the brain and could be widely applied to new therapeutic NSC-based therapies for neurodegenerative
diseases.

## Key facts

- **NIH application ID:** 9832684
- **Project number:** 5R03NS106629-02
- **Recipient organization:** ROSKAMP INSTITUTE, INC.
- **Principal Investigator:** MARGARITA GUTOVA
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $80,000
- **Award type:** 5
- **Project period:** 2018-12-15 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832684

## Citation

> US National Institutes of Health, RePORTER application 9832684, Development of Neural Stem Cell mediated therapy for repetitive mild TBI. (5R03NS106629-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9832684. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*