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Strategies to Enhance Engineered Heart Tissue Based Myocardial Repair

Award Number: R01HL162747
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Strategies to Enhance Engineered Heart Tissue Based Myocardial Repair - PROJECT SUMMARY Ischemic heart disease, such as unstable coronary angina or myocardial infarction, often leads to systolic heart failure due to the loss of contractile cardiomyocytes. Engineered heart tissue mediated transplantation of stem cell derived cardiomyocytes holds the promise to regenerate the myocardium and improve cardiac function post myocardial infarction in preclinical animal models. Despite these encouraging results, several critical barriers limit the clinical application of engineered heart tissue-based therapy. For example, the poor perfusion in the infarct area compromises the survival of transplanted cardiomyocytes. In addition, the procedure of transplantation of engineered heart tissue typically requires open chest surgery which is a significant challenge to the patients with severe heart failure. Data from our previous studies showed that promoting cell cycle and proliferation in human induced pluripotent stem cells (hiPSC-CMs) constitutes a viable approach to enhance engraftment and restore function in ischemic heart disease. We also generated a new type of nanoparticles that enable myocardial protection via increased vasculogenesis in the ischemic heart. Furthermore, we established an injectable and shape-recoverable tissue with GelMA-coated nanofiber scaffolds. In this project, we aimed to develop novel approaches to enhance the engraftment of implanted hiPSC-CMs via integrating nanomaterials, cell- and tissue-engineering technologies. Specifically, we will 1) develop a novel engineered heart tissue which leverages the capacity of nanomaterials to release pro-vasculogenic molecules and promote revascularization in these engineered heart tissues and in the infarct heart; 2) take the advantage of our recently established protocol to induce the proliferation of survival cardiomyocytes inside the engineered heart tissues; and 3) study if delivery of these novel engineered heart tissues to animals with acute or chronic myocardial infarction leads to robust myocardial regeneration and repair.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $652,089 )
2025	2025	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cardiovascular Diseases Research	000	3	11/9/2024	NON-COMPETING CONTINUATION	$652,089
														Subtotal = $652,089

Issue Date FY: 2024 ( Subtotal = $710,051 )
2024	2024	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cardiovascular Diseases Research	001	2	6/26/2024	NON-COMPETING CONTINUATION	$57,962
2024	2024	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cardiovascular Diseases Research	000	2	1/4/2024	NON-COMPETING CONTINUATION	$652,089
														Subtotal = $710,051

Issue Date FY: 2023 ( Subtotal = $762,200 )
2023	2023	MAYO CLINIC ARIZONA	13400 E SHEA BLVD	SCOTTSDALE	AZ	85259	MARICOPA	USA	Cardiovascular Diseases Research	000	1	12/9/2022	NEW	$762,200
														Subtotal = $762,200

Grand Total All Awards = $2,124,340

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Strategies to Enhance Engineered Heart Tissue Based Myocardial Repair

Award Number: R01HL162747

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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