# Multimodality Molecular Imaging of Stem Cell Therapy for Ischemic Cardiomyopathy

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $430,736

## Abstract

PROJECT ABSTRACT
Receiving this New and Early Investigator R01 grant will help me complete my transition into an independent
physician-scientist who applies advanced imaging technology to translate novel therapy to the bedside. As a
cardiovascular medicine specialist with extensive training in multi-modality imaging and stem cell biology, I am
in a unique position to apply my expertise to overcome important hurdles that continue to hinder the routine
clinical implementation of cardiac stem cell regenerative therapy for ischemic heart disease.
End-stage heart failure from ischemic heart disease remains a devastating disease with high morbidity and
mortality. It is estimated that one in nine death results from heart failure. Although cardiac stem cell therapy
has emerged as a promising therapy to repair or replace the damaged myocardium, results from large,
randomized clinical trials using bone marrow derived stem cells have shown that only a few patients benefit.
These disappointing results have fueled criticism from nonbelievers that these cells cannot regenerate the
heart. It is possible, however, that these cells never reach the injured myocardium or die before they can
significantly improve heart function. Clearly, we need to incorporate advanced imaging techniques to visualize
stem cell fate after transplantation to gain a better understanding of why clinical trials have shown that cardiac
stem cell therapy benefits only a few patients.
The long-term goal of this proposal is to apply novel techniques in genome editing and multi-modality imaging
to facilitate stem cell trafficking in humans in the near future. In Aim 1 of this proposal, we will use novel site-
specific genome editing techniques (e.g., CRISPR) to introduce a human reporter gene, which is potentially
less immunogenic, into human induced pluripotent stem cells (hiPSCs) for cell trafficking. In Aim 2, we will
transplant cardiomyocytes differentiated from iPSCs (iPSC-CMs) carrying the reporter gene with and without
pre-treatment with pro-survival agents into a rat model of myocardia infarction. We will perform in vivo tracking
of cell survival and correlate survival curves with functional improvement. We will use molecular imaging as
well as transcriptional, proteomic, and histological assays to better understand the mechanisms contributing to
acute donor death and determine if the administration of adjuvant agents can improve cell survival. In Aim 3,
we will determine whether the best adjuvant therapy identified in Aim 2 will also improve cell survival in a
porcine model of ischemic cardiomyopathy. We will optimize imaging and treatment protocols in this large
animal model, which is necessary before initiating reporter gene imaging in humans. Information from these
studies will lay the foundation for our group and others to incorporate cardiac stem cell imaging into clinical
trials.

## Key facts

- **NIH application ID:** 9991887
- **Project number:** 5R01HL134830-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Patricia Kim Phuong Nguyen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $430,736
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991887

## Citation

> US National Institutes of Health, RePORTER application 9991887, Multimodality Molecular Imaging of Stem Cell Therapy for Ischemic Cardiomyopathy (5R01HL134830-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9991887. Licensed CC0.

---

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