# Endogenous and exogenous mechanisms that promote myocardial remuscularization in post infarction LV remodeling

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $519,750

## Abstract

Endogenous and exogenous mechanisms that promote myocardial remuscularization in post
 infarction LV remodeling
Summary / Abstract
 The molecular and cellular basis for the progressive heart failure is the result of the inability of damaged
and apoptotic myocytes to be replaced. While a number of cell- and tissue-based therapies can limit this
dysfunction, the proportion of cells that survive at the site of administration for more than a few weeks after
transplantation is extremely low. As such, substantial remuscularization of the infarcted region has rarely
been reported; and when limited remuscularization has been reported, it is frequently accompanied by
potentially lethal ventricular arrhythmias of unknown mechanism. This proposal aims at remuscularization of
the injured ventricle from “within” by identifying key regulators of the cell cycle and by promoting the native
cardiomyocyte (CM) reenter the cell cycle, and from “outside” by transplanting bioengineered cardiac muscle
patch (hCMP) with the key regulators of CM cell cycle upregulated, and with that incorporate a functional
vascular network and recapitulate some of the key micro environmental cues of native heart tissue. We
recently established a novel hiPSC cell line with MHC-driven overexpression of a key regulator of CM: CCND2
(hiPSC-MHC-CCND2OE), which can remuscularize injured ventricle in rodent model. The central objective of
this proposal is to “turn back the clock” of myocyte cell cycle for myocardial repair. The specific Aims ( SA) are:
SA1: Identifying the key regulators that promote cell-cycle activity in the hearts of early neonatal pigs after
myocardial injury. We will: 1) using state-of-the-art molecular biology and imaging technologies, and the single
cell/nucleus RNA sequencing (scRNAseq or snRNAseq) technology to demonstrate these key
regulators/signaling pathways that control the myocyte cell cycle; and2) test remuscularization of injured
ventricle by manipulating the key regulators using either targeted modRNA or AAV9 to selectively modify these
regulators in adult pigs with AMI. SA2a. Engineering hCMPs of previously unattainable size and thickness
that are functionally mature and primed for in-vivo vascularization. SA2b. Evaluating the effectiveness of our
hCMP constructs for myocardial recovery and remuscularization in a large-animal (swine) model of myocardial
injury. We will use state-of-the-art techniques of optical mapping in combination with the 3-dimensional
intramural cardiac mapping to delineate potential arrhythmia mechanisms over the entire left-ventricular
surface and transmurally.

## Key facts

- **NIH application ID:** 10302748
- **Project number:** 2R01HL114120-10
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Jianyi Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $519,750
- **Award type:** 2
- **Project period:** 2012-08-10 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302748

## Citation

> US National Institutes of Health, RePORTER application 10302748, Endogenous and exogenous mechanisms that promote myocardial remuscularization in post infarction LV remodeling (2R01HL114120-10). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10302748. Licensed CC0.

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