# Temporospatial Single-Cell Characterization of Angiogenesis and Myocardial Regeneration in Small and Large Mammals

> **NIH NIH F32** · STANFORD UNIVERSITY · 2023 · $76,052

## Abstract

Project Summary/Abstract
Ischemic heart disease affects more than 197 people worldwide every year. Despite advances in macro
revascularization techniques such as coronary artery bypass grafting and percutaneous coronary intervention,
many patients progress to heart failure due to residual microvascular perfusion deficits. Although the adult human
heart appears to be unable to significantly regenerate myocardium after injury, neonatal mice and pigs are
capable of efficient angiogenesis and myocardial regeneration during the first week of life. Endogenous
angiogenic and regenerative pathways are intricately linked to the wound-healing inflammatory cascade,
extracellular matrix remodeling, endothelial cell migration, and cardiomyocyte proliferation. Consequently, the
infarct border zone, which is the spatial intersection of these cellular processes, has proven to be a complex and
dynamic microenvironment to investigate. In this proposal, we describe a novel application of a multiplexed
immunofluorescent imaging platform with single cell resolution called CODEX (co-detection by indexing) which
was developed here at Stanford. With the guidance and mentorship described in the research training plan, we
have compiled an advisory committee of physician and surgeon-scientists, cardiologists, cell biologists, and the
experts in CODEX from Stanford's Cell Sciences Imaging Facility. If awarded this Fellowship, this
multidisciplinary team is uniquely positioned to execute this first of its kind application of CODEX to myocardial
regeneration. CODEX will be used to characterize the longitudinal changes in the spatiotemporal relationship
between the resident cells of the myocardium and the paracrine pathways that govern angiogenesis and
myocardial regeneration. CODEX is an extension of immunofluorescence microscopy that utilizes antibodies
conjugated to DNA barcodes to simultaneously quantify up to 44 antigens in situ. In Aim 1 we will apply CODEX
to neonatal mouse and pig LAD ligation models of myocardial regeneration to define novel spatial phenotypes
of angiogenic and inflammatory cellular neighborhoods throughout the neonatal period of regenerative potential
in comparison to non-regenerating adults. After characterizing the cellular microenvironments and cell-signaling
activity of natural angiogenesis in neonatal mammals, in Aim 2 we will investigate the effect of exogenous
modulators of angiogenesis and the acute inflammatory response in adult mice and pigs. As an animal model
for myocardial regeneration, the regulatory pathways that govern natural angiogenesis and subsequent
myocardial regeneration in the mouse and pig are the subject of great interest due to their potential therapeutic
benefit in humans. By using CODEX to study the complex interplay between multiple cell types, paracrine
signaling pathways, and intercellular processes we hope to advance our mechanistic understanding of natural
neonatal angiogenesis and myocardial regeneration and identif...

## Key facts

- **NIH application ID:** 10751870
- **Project number:** 1F32HL170741-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Stefan Elde
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $76,052
- **Award type:** 1
- **Project period:** 2023-08-10 → 2025-08-09

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751870

## Citation

> US National Institutes of Health, RePORTER application 10751870, Temporospatial Single-Cell Characterization of Angiogenesis and Myocardial Regeneration in Small and Large Mammals (1F32HL170741-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10751870. Licensed CC0.

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