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Development and validation of a novel bioprinted, human-diabetic cardiac organoid model

Award Number: SC1HL154511
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Development and validation of a novel bioprinted, human-diabetic cardiac organoid model - Cardiomyopathy is a debilitating complication of type-2 diabetes that predisposes patients towards increased risk of heart failure due to the disorder of the heart muscle that compromises its ability to circulate blood through the body and maintain a normal electrical rhythm, effectively. Despite its immense clinical impact, there is a lack of targeted treatment regimen for diabetic cardiomyopathy due to the intricate pathophysiology of the condition that makes drug screening problematic. Current therapeutic strategies developed on results originating from animal experiments, do not transform well to humans in vivo. Hence, studies should be based on laboratory engineered ‘cardiac tissue’ models biofabricated from human induced pluripotent stem cell (iPSC) differentiated cardiomyocytes that are essential to preserve in vivo physiology, and mimic disease progression. But, there is lack of such preclinical human tissue based models to establish a screening platform for the identification of potential therapeutics that will preserve cardiac cell physiology and function when exposed to diabetic stress. To address this need, we will develop a unique ‘cardiac organoid’ system that will be assembled using bioprinting of human cardiac cells, including cardiomyocytes (CM), fibroblasts (CF) and endothelial cells (EC), specifically sourced from diabetic donors. Bioprinting will enable the creation of an environment to nurture the development of physiologically relevant cues, resulting in a functional tissue construct with appropriate consistency. Cells derived from diabetic donors will retain their disease phenotype or `metabolic memory', which will be valuable to observe and study their structural and functional changes when exposed to hyperglycemic environments. Human iPSC sourced from type-2 diabetic donors will be custom differentiated into CM and mixed with CF and EC for bioprinting of ‘cardiac organoids’ that will be exposed to normal and hyperglycemic conditions to delineate between the effects caused by metabolic memory, hyperglycemia and a combination of both. Results will help in understanding the role of the signaling pathways involved in disease progression, which may guide and inform us towards designing an enhanced therapeutic approach for rescuing cardiac tissues from hyperglycemic insult. The successful completion of these studies will lead to establishment of a patient-specific iPSC model of human type-2- diabetes, and reveal the power of this approach for discovery of new therapeutic strategies for a complex metabolic condition with rising clinical significance.


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: 2026 ( Subtotal = -$2,278 )
2026	2023	THE UNIVERSITY OF TEXAS AT EL PASO	500 W UNIVERSITY AVE	EL PASO	TX	79968	EL PASO	USA	Cardiovascular Diseases Research	000	4	3/24/2026	NON-COMPETING CONTINUATION	-$2,278
														Subtotal = -$2,278

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	THE UNIVERSITY OF TEXAS AT EL PASO	500 W UNIVERSITY AVE	EL PASO	TX	79968	EL PASO	USA	Cardiovascular Diseases Research	000	4	9/16/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $302,000 )
2023	2023	UNIVERSITY OF TEXAS AT EL PASO	500 W UNIVERSITY AVE	EL PASO	TX	79968	EL PASO	USA	Cardiovascular Diseases Research	000	4	8/15/2023	NON-COMPETING CONTINUATION	$302,000
														Subtotal = $302,000

Issue Date FY: 2022 ( Subtotal = $302,000 )
2022	2022	UNIVERSITY OF TEXAS AT EL PASO	500 W UNIVERSITY AVE	EL PASO	TX	79968	EL PASO	USA	Cardiovascular Diseases Research	000	3	8/21/2022	NON-COMPETING CONTINUATION	$302,000
														Subtotal = $302,000

Issue Date FY: 2021 ( Subtotal = $302,000 )
2021	2021	UNIVERSITY OF TEXAS AT EL PASO	500 W UNIVERSITY AVE	EL PASO	TX	79968	EL PASO	USA	Cardiovascular Diseases Research	000	2	8/28/2021	NON-COMPETING CONTINUATION	$302,000
														Subtotal = $302,000

Issue Date FY: 2020 ( Subtotal = $297,920 )
2020	2020	UNIVERSITY OF TEXAS AT EL PASO	500 W UNIVERSITY AVE	EL PASO	TX	79968	EL PASO	USA	Cardiovascular Diseases Research	000	1	9/11/2020	NEW	$297,920
														Subtotal = $297,920

Grand Total All Awards = $1,201,642

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Development and validation of a novel bioprinted, human-diabetic cardiac organoid model

Award Number: SC1HL154511

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/15/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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