# Reverse Tissue-Manufacturing of the Multicellular Sinoatrial Node Organoids

> **NIH NIH R01** · EMORY UNIVERSITY · 2023 · $610,803

## Abstract

Project Summary/Abstract
 The recent increasing prevalence, severity, and healthcare burden of sinoatrial (SA) node dysfunction
emphasize the need for more detailed studies of SA node functions that allow for effective therapy to treat and
prevent SA node dysfunction. The major mechanisms of the dysfunction are the impaired ability of pacemaker
cells to induce spontaneous rhythm (automaticity) and adverse remodeling in their electric conduction to
surrounding atrial tissues (SA conduction). However, the current SA node or pacemaker models have been
limited to theoretical models and isolated single cell-type cells or cell clusters, leaving a gap to model the
autonomous cardiac contraction and heart rhythm and dysfunctions in automaticity and SA conduction. Moreover,
the current single cell-type pacemakers worsened heart rhythm stability during one-month in vivo integration,
which limits its application as a clinically viable biological pacemaker capable of generating robust pacemaking
and conduction.
 To address the current limitation of SA node models, this proposal aims to develop a three-dimensional
multicellular SA node organoid by reproducing human SA node’s multicellular tissue structure and fail-safe
mechanisms. In contrast to the single cell-type biological pacemakers, human SA node is a natural organoid with
elaborate insulated architecture and heterogeneous cellular composition. Moreover, the human SA node is
equipped with redundant pacemaker sites and conduction pathways to protect the rhythm against adverse
chronotropic stimulations. Thus, inspired by SA node’s structure and fail-safe mechanism, we aim at enhancing
robustness in both automaticity and SA conduction: First, we will focus on enhancing automaticity of SA
node organoids by identifying the expression of pacemaker membrane and calcium clock proteins, cell
composition, and shape (Aim 1). Second, we will concentrate on improving conduction of SA node organoids
by coordinating multiple pacemaker sites and conduction pathways (Aim 2). Last, we will evaluate the
robustness of the SA node organoids in in vitro setting and in vivo atrioventricular block rodent model (Aim 3).
 These studies will define if tissue-level architecture and multicellular compositions mediate SA node’s robust
pacemaking and conduction and may reveal a high-fidelity tissue-level biological pacemaker as a novel
therapeutic strategy for SA node dysfunctions. The proposed organoids will be suitable for human preclinical
testing assays to accelerate drug development, for dissecting patient-specific SA node disease pathophysiology,
and for the development of implantable biological pacemakers.

## Key facts

- **NIH application ID:** 10660542
- **Project number:** 1R01HL161366-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Sung Jin Park
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $610,803
- **Award type:** 1
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10660542

## Citation

> US National Institutes of Health, RePORTER application 10660542, Reverse Tissue-Manufacturing of the Multicellular Sinoatrial Node Organoids (1R01HL161366-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10660542. Licensed CC0.

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