# ENHANCING CARDIOPOIETIC REGENERATION FOR ISCHEMIC CARDIOMYOPATHY

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2021 · $397,500

## Abstract

PROJECT SUMMARY
Acute survival following myocardial infarction has precipitated a growing heart failure epidemic, warranting de-
velopment of disease-altering treatments to restore tissue integrity and ventricular function. The homeostatic
capability for self-renewal in the adult human heart is insufficient in the setting of myocardial injury. Adult stem
cell therapies, conceived to bolster this innate regenerative reserve and achieve clinically meaningful cardiac
regeneration, have been found safe but demonstrate inconsistent benefit in ischemic cardiomyopathy. This
recognized roadblock impedes the roll-out of cardiac regenerative medicine in clinical practice. To prime re-
generative proficiency, our team initially introduced the lineage-specifying cardiopoiesis platform. Despite this
optimization, a range of benefit following cardiopoietic stem cell therapy was experienced in two separate clini-
cal trials. Exploiting the C-CURE and CHART-1 trial experience, preliminary work documented an altered mi-
croRNA and secretome landscape germane to cardiopoietic stem cells that yielded the best outcomes in hu-
man testing. Use of clinical readouts in conjunction with systems biology deconvolution of trial-biobanked car-
diopoietic stem cell samples underpins an innovative approach to target pathways that drive regenerative ac-
tion. The overarching hypothesis of the present proposal is that the molecular roadmap segregating high re-
generative properties can be actuated to reverse engineer stem cells featuring enhanced regenerative profi-
ciency. Thus, a clinical trial-informed paradigm is here introduced to dial-up the regenerative aptitude of stem
cells. The proposal aims to: (1) engineer a highly regenerative cardiopoietic (hrCP) phenotype through targeted
microRNA programming to achieve enhanced regenerative efficacy tested in murine ischemic cardiomyopathy;
(2) establish mechanisms underlying hrCP action through a proteomic systems approach resolving impact on
the disease substrate with focus on neovasculogenesis as a prioritized tissue compartment in repair; and final-
ly (3) scale-up hrCP for translation in a porcine model of ischemic heart failure with molecular and functional
imaging tracking biodistribution and therapeutic effectiveness, along with histological and high-throughput
analysis, to demonstrate bioequivalency in clinically relevant conditions. Timely execution of stated aims is fa-
cilitated by a multidisciplinary team with a track record in translating stem cell innovation, established method-
ologies and resources, and a body of supporting preliminary work. On completion, the proposed research will
realize the prospect of a clinomics-informed evolution in stem cell therapy for ischemic heart failure delivering
an engineered and validated highly regenerative biotherapy.

## Key facts

- **NIH application ID:** 10073349
- **Project number:** 5R01HL134664-04
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** ANDRE TERZIC
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $397,500
- **Award type:** 5
- **Project period:** 2017-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073349

## Citation

> US National Institutes of Health, RePORTER application 10073349, ENHANCING CARDIOPOIETIC REGENERATION FOR ISCHEMIC CARDIOMYOPATHY (5R01HL134664-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073349. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*