# Multimodal approach investigating the immunomodulatory effect ofneural stem cells in stroke recovery

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $629,968

## Abstract

Human neural stem cell (hNSC) therapy for stroke is showing promise as it moves from the
bench into early clinical trials to treat the long term disabilities resulting from stroke. This
provides hope for the millions of Americans living with the chronic, debilitating effects of stroke.
Major questions remain, however, about how stem cells injected into the brain drive stroke
recovery. A clue to stem cell mechanism of action is the recent discovery of the positive
correlation between stroke recovery and a brain MRI signal – T2-FLAIR signal– in stroke
patients treated with stem cells. We have successfully reproduced this stem cell-induced FLAIR
signal in stroke-injured rats, and shown that its associated with inflammation. This led to our
central hypothesis: stem cell transplantation drives recovery by inducing a regenerative
inflammatory response. The objective of this grant is to use a rat model of subcortical stroke to
investigate the immunomodulatory effects of hNSC transplanted at the chronic stage of stroke,
at the regional, cellular and molecular levels using a multimodal approach. In Aim1 we use MRI
and PET imaging to identify which brain regions show inflammatory changes after hNSC
transplantation, and which inflammatory regions best correlate with recovery. This will also test
the utility of these clinically relevant imaging modalities as biomarkers for stroke recovery. In
Aim 2 we identify the immune changes induced by hNSC treatment using multiple tools to
characterize the types and molecular signatures of the immune cells present, and their spatial
interactions. In Aim 3 we determine which hNSC-secreted factors modulate the immune
response by testing several candidates, in vitro and in vivo, using CRISPR tools to modulate
expression of key candidate factors. We will study the impact of manipulating the levels of these
proteins on stroke recovery and immunomodulation. Upon conclusion of the study, we will have
made significant advancements in understanding how hNSC-induced immunomodulation affects
brain repair. This contribution is significant because it will: a) identify potential biomarkers, both
pre- and post-treatment, for hNSC-induced recovery; b) begin to delineate the molecular
pathways involved in brain repair; and c) ultimately lead to identification of novel therapies for
stroke.

## Key facts

- **NIH application ID:** 9917846
- **Project number:** 5R01NS058784-10
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** GARY K STEINBERG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $629,968
- **Award type:** 5
- **Project period:** 2008-08-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917846

## Citation

> US National Institutes of Health, RePORTER application 9917846, Multimodal approach investigating the immunomodulatory effect ofneural stem cells in stroke recovery (5R01NS058784-10). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9917846. Licensed CC0.

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