# Injectable Hydrogels to Deliver Gene Therapy for Myocardial Infarct

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $28,965

## Abstract

Project Summary
Stromal derived factor-1α (SDF-1α) rapidly increases following myocardial infarction (MI) and has been shown
to increase microvascular density, reduce infarct size, inhibit border zone expansion, and attenuate adverse
remodeling to preserve the ischemic cardiac tissue. However, this intrinsic upregulation is transient, and the
protective function of SDF-1α quickly declines, thereby reducing the potential for tissue repair. To combat this
limitation, several groups have investigated the exogenous delivery of SDF-1α. It was found that early-stage
delivery of exogenous SDF-1α augmented the endogenous repair process, while late-stage increase in SDF-1α
was shown to improve cardiac function. These studies motivate a therapeutic approach to provide sustained
SDF-1α delivery and functional benefit, which is investigated in the parent project.
 Despite encouraging results from short-term exogenous SDF-1α delivery, little is known about the effects
of sustained SDF-1α delivery into the myocardium following acute MI. Further investigation of these effects is an
important logical extension and integral component of the parent project, as it may be completely distinct from
the effects of short-term treatment with SDF-1α. Further, while single delivery of SDF-1α gene therapy is already
in clinical studies and demonstrate promising results, these therapies were delivered in saline. Therefore,
lingering questions remain as to whether repeated delivery of the gene therapy would further improve cardiac
function. For sustained delivery of SDF-1α to enter clinical studies, additional information is necessary to better
understand its effects, mechanism of action, as well as any possible adverse effects.
 Towards this goal, we propose an extension to Aim 3 of the parent project. There, we proposed to use
the elastin-like protein-hyaluronic acid (ELP-HA) hydrogel formulation, which has been optimized in vitro for
sustained SDF-1α minicircle (MC) gene release, in an in vivo preclinical assessment of cardiac function recovery.
In this Diversity Supplement project, we will evaluate the in vivo vascular regeneration of the heart following MI
through immunohistochemistry of cardiac tissue. To investigate possible mechanism(s) of any regeneration that
we see, we will perform proteomic profiling of cytokine secretions as well as RNA sequencing (RNASeq). Finally,
since SDF-1α and its receptor CXCR4 is known to play an important role in stem cell homing to the ischemic
myocardium, we will investigate its chemoattractive potential to draw endogenous endothelial progenitor cells
(EPCs). The results of our study will inform us not only if sustained delivery of SDF-1α is beneficial to vascular
and cardiac regeneration following MI, but also the mechanism by which SDF-1α delivers its benefits. This
Diversity Supplement will advance the research career of an underrepresented minority trainee towards the
transition to independence.

## Key facts

- **NIH application ID:** 10732139
- **Project number:** 3R01HL151997-03S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Sarah C Heilshorn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $28,965
- **Award type:** 3
- **Project period:** 2023-02-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10732139

## Citation

> US National Institutes of Health, RePORTER application 10732139, Injectable Hydrogels to Deliver Gene Therapy for Myocardial Infarct (3R01HL151997-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10732139. Licensed CC0.

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