# Enhancement of Cardiac Cell therapy by reintroduction of developmental signaling

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $390,000

## Abstract

Project summary
Ischemic heart disease (IHD) is a major cause of morbidity and mortality in the US. Adult heart
is largely dormant, designed primarily to perform pump function and responding to pathological
challenge by limited myocyte turnover with development of scar tissue at the site of injury.
Incredibly, cardiac tissue during developmental stages consists of actively diving
cardiomyocytes and is able to resolve injury by formation of new tissue. The fundamental
question is whether adult heart can be somehow driven into a developmental signaling state
restoring cellular replacement without compromising pump function. Cardiac progenitor cell-
based (CPC) applications have been widely used to resurrect myocardial repair processes and
have moved into clinic but are limited due to underperformance of the donated cells. In most
cases, CPCs are harvested from elderly patients with an adverse cardiac tissue morphology
including host of clinical features reducing therapeutic efficacy of the cells and their cell-free
agents such as exosomes. Interestingly, CPCs are known to possess incredible growth and
repair properties during fetal and neonatal cardiac stages and understanding unique signaling
hubs regulating CPC performance during development may open up a novel avenue for
enhancement of CPC therapy. Ideally changing cardiac microenvironment to resemble a
developmental cardiac tissue may offer a powerful way to restore lost cardiac repair ability. Our
preliminary data indicates miR-294 signaling axis enhances cardiac performance including core
CPC function mediated by its downstream target Lin28a. Therefore, we hypothesize that
reintroduction of developmental miR-294-Lin28a signaling axis in CPCs will promote CPC
properties reminiscent of more primitive developmental stage where the heart can better repair
itself. Our goal is to enhance CPC therapy including the potency of cell-free agents such as
exosomes by induction of developmental signaling to repair the heart after myocardial damage.
We will extend these studies to develop a therapeutic strategy on miR294-Lin28a based
modification of human heart derived CPCs and their exosomes that enhances cardiac structure
and function after injury. Enhancement of cardiac cell therapy by reintroduction of
developmental signaling provides a new direction for CPC based cell therapeutics and
treatment of heart failure.

## Key facts

- **NIH application ID:** 9837472
- **Project number:** 5R01HL135117-04
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Mohsin Khan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $390,000
- **Award type:** 5
- **Project period:** 2016-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9837472

## Citation

> US National Institutes of Health, RePORTER application 9837472, Enhancement of Cardiac Cell therapy by reintroduction of developmental signaling (5R01HL135117-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9837472. Licensed CC0.

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