# Autologous Cardiomyocytes from Masseter Muscles to Repair Myocardial Infarction (MI)

> **NIH NIH R01** · UNIVERSITY OF CINCINNATI · 2020 · $446,160

## Abstract

Abstract
Myocardial infarction (MI) is caused by lack of adequate blood flow to the heart and results in terminal loss
of cardiomyocytes (CM). MI and its related complications are a leading cause of death worldwide. The
search for regenerative therapy that can repair or replace lost CM remains a daunting challenge. The
foremost issue is the difficulty in procuring viable replacement cells. Heterologous sources are unattractive
due to the potential for immunorejection. Harvesting progenitor cells from a patient's damaged heart is
invasive and poses severe risks. Reprogramming somatic cells from other autologous sources can result in
very low yields due to genetic or epigenetic barriers. A series of recent studies, however, has revealed that
masseter muscle derived progenitor (MMP) cells share a common origin and have overlapping gene
expression patterns with heart muscle. MMP can be isolated from highly accessible masseter muscles
without mandible motor dysfunction and our preliminary data has shown that MMP yield the highest rate of
CM differentiation as compared with limb muscle progenitors. Importantly, MMP can give rise to functional
CM phenotypes including ventricular, atrial, and pacemaker CM under defined conditions. Therefore, MMP
represent an ideal therapeutic candidate to maximize cardiogenic differentiation efficiency after cell
transplantation in order to repopulate an infarcted heart region with a supply of autologous CM. At the
same time, MMP avoid the common pitfalls associated with immunorejection, tumor formation, and
reversion to an alternative epigenetic precursor. Aim 1 consists of in vitro studies to isolate and
characterize MMP (including developmental origin, surface markers, and proliferation potential) in order to
gain the desired CM population using novel sorting approaches. Aim 2 is designed to determine the
mechanism by which microRNAs and transcription factor networks mediate the lineage commitments of
MMP and the underlying cardiac potential of MMP as regulated by miR-128. Finally, Aim 3 focuses on the
effects of implantation of MMP-derived cell sheets on the cardiac functions in mouse and porcine MI
models. Experiments will examine the in vivo cell fate of MMP and determine any beneficial effects that
result from cell engraftment and functional integration under ischemic conditions. These studies will provide
new insights in both basic heart developmental biology and cell-based regenerative medicine. This
approach holds great promise for the emerging field of personalized medicine and strongly supports the
possibility that autologous MMP harvested from human masseter muscles and expanded in vitro will serve
as a major source of CM that will be highly effective for treatment of patients after MI.

## Key facts

- **NIH application ID:** 9846234
- **Project number:** 5R01HL136025-04
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** W Sean Davidson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $446,160
- **Award type:** 5
- **Project period:** 2017-02-06 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9846234

## Citation

> US National Institutes of Health, RePORTER application 9846234, Autologous Cardiomyocytes from Masseter Muscles to Repair Myocardial Infarction (MI) (5R01HL136025-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9846234. Licensed CC0.

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