# Reshaping MSC surface expression profiles to target inflammation following CNS trauma

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $434,394

## Abstract

Project Summary/Abstract
Traumatic brain injury (TBI) is a leading cause of death and disability with approximately 1.7
million incidents annually at a total cost of over $76 billion in 2000 according to the Center for
Disease Control and Prevention. There is an urgent need to develop new treatments that will
limit secondary injury associated with inflammation, decrease blood-brain barrier permeability,
increase neurogenesis, and overall improve clinical outcome in TBI. To that end, cell therapies
using mesenchymal stem cells (MSC) and MSC-like cells have demonstrated some efficacy in
pre-clinical models and similar indications. There are a number of technical challenges in using
cell therapies to treat traumatic injuries, such as their rapid clearance from circulation and a
limited ability to home to sites of injury and the brain. Our team has developed a set of
bioengineering tools to precisely control the expression of multiple genes integrated into a
landing pad. Here we propose to combine this new technology with our ongoing studies of MSC
as a promising therapeutic for TBI. Specifically we propose to express a combination of an
important damage homing protein (CXCR4) and a leukocyte adhesion molecule (PSGL-1) along
with an enzyme that increases PSGL-1 binding affinity to markers of injury and inflammation
(FUT7/SLeX). We will test different levels of expression in combination to select populations of
MSC that are specified to detect damaged endothelia in vitro and then in vivo in order to
increase the localization of MSC to the CNS following TBI. We hypothesize that by increasing
the homing and attachment of MSC to injured tissue, we can increase the efficiency of several
key mechanisms of action used by MSC to improve TBI outcomes, such as local paracrine
support and modulation of immune cell activity. This study includes a proof-of-concept
experiment utilizing an animal model of TBI, where modified MSC are tested for the ability to
improve both short-term biomarkers of injury and long-term behavioral outcome measures of
memory and cognition. The successful completion of this study will demonstrate that we can
specifically target MSC to inflamed endothelia, increase the potency of MSC to treat TBI, and
prove a novel bioengineering approach can significantly advance the translational applications
of cell therapies.

## Key facts

- **NIH application ID:** 9958590
- **Project number:** 1R21NS116302-01
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Scott D Olson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $434,394
- **Award type:** 1
- **Project period:** 2020-04-01 → 2022-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958590

## Citation

> US National Institutes of Health, RePORTER application 9958590, Reshaping MSC surface expression profiles to target inflammation following CNS trauma (1R21NS116302-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/9958590. Licensed CC0.

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