# Creating Endogenous Stem Cell Niches to Promote Functional Brain Repair Post-TBI

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2021 · $312,797

## Abstract

PROJECT SUMMARY
Traumatic Brain Injuries (TBIs) result in a range of complex neurophysiological and functional deficits, severe long-term
disability, and poor prognosis for the affected individuals. The significant brain tissue loss encountered post-TBI is a major
contributor to these poor outcomes. Current interventions that target single components of TBI related trauma have largely
failed to prevent widespread brain tissue loss and promote repair and functional recovery. Transplanted and host Neural
Stem Cells (NSCs) possess multifaceted therapeutic potential, owing to their ability to produce efficacious amounts of
neuroprotective factors in addition to facilitating complex large-scale repair and reconstruction of damaged brain tissue.
However, current strategies fail to augment endogenous NSC and trophic factor activity necessary to promote long-lasting
repair and recovery after a moderate-to-severe TBI. We hypothesize that the transplantation of allogeneic exogenous NSCs
in a selectively engineered glycomaterial matrix capable of attracting and retaining endogenous NSCs and protective factors
will facilitate functional repair of brain tissue post TBI. The creation of an ectopic NSC niche as proposed here can maintain
NSCs in their undifferentiated state, and help confer neuroprotection and preservation of function chronically post-TBI.
Toward this goal, we will exploit the unique structural and functional attributes of Chondroitin Sulfate Glycosaminoglycan
(CS-GAG) sulfation to design novel engineered CS-GAG (eCS-GAG) matrices that are capable of enriching trophic factors,
and maintaining transplanted and host NSCs in their undifferentiated state. We will implant eCS-GAG matrices either alone
or in combination with NSCs in a rodent model of moderate-to-severe TBI. We will evaluate the enhanced potential of
trophic factor enriching eCS-GAG matrices to promote NSC self-renewal and facilitate neuroprotection and functional
recovery chronically post-TBI when compared to other sulfated and unsulfated GAG matrix controls. Our approach is novel
in that it exploits the compositional and functional diversity of CS-GAG sulfation to facilitate the haptotaxis of endogenous
NSCs, and presentation of endogenous protective factors within the engineered chemistry of the matrix to significantly
improve NSC efficacy after moderate-to-severe TBI.

## Key facts

- **NIH application ID:** 10207793
- **Project number:** 5R01NS099596-05
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Lohitash Karumbaiah
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $312,797
- **Award type:** 5
- **Project period:** 2017-07-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207793

## Citation

> US National Institutes of Health, RePORTER application 10207793, Creating Endogenous Stem Cell Niches to Promote Functional Brain Repair Post-TBI (5R01NS099596-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10207793. Licensed CC0.

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