Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Technologies enabling robust closed-loop manufacturing of human pluripotent stem cell-derived cardiomyocytes

Award Number: R01HL178095
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2025
PERIOD OF PERFORMANCE END DATE: 11/30/2028

Group Awards By:

View Award Description

Technologies enabling robust closed-loop manufacturing of human pluripotent stem cell-derived cardiomyocytes - PROJECT SUMMARY Cell therapy is a rapidly growing field, with Chimeric Antigen Receptor T (CART) cells and stem cell-based therapies showing remarkable efficacy in treating hematologic cancers and regenerating tissue for conditions like Parkinson’s Disease, blindness, type 1 diabetes, and heart failure. However, manufacturing cellular therapies is complex, resulting in high costs and variable product quality. This study aims to address these challenges by developing feedback-controlled closed-loop processes for differentiating human pluripotent stem cells (hPSCs) into cardiomyocytes (CMs). Despite advancements in hPSC-CM differentiation processes over the past decade, enabling their adoption in various applications, including human development studies, disease modeling, drug screening, and clinical trials for heart failure treatment, significant variability exists between batches and cell lines during manufacturing. This variability becomes more pronounced with the transition from 2D to 3D platforms. Building on preliminary data comparing successful and failed hPSC differentiation batches that identified genetic and epigenetic features predictive of CM generation, notably variations in WNT and MAPK signaling in cardiac progenitor cells (CPCs), this study aims to develop control strategies to enhance differentiation reproducibility across various conditions. This project's overarching goal is to improve the robustness and reproducibility of hPSC differentiation into CMs through feedback-controlled closed-loop manufacturing processes. Leveraging single-cell transcriptomics and epigenomics, our project will gain a deep understanding of differentiation failure modes, enabling early identification and correction of process deviations. The proposed aims are: Aim 1: Identify 2D CM differentiation failure modes through integrated single-cell transcriptomics and epigenomics. Single-cell RNA sequencing (scRNAseq) and transposase-accessible chromatin sequencing (ATACseq) performed throughout CM differentiation runs and analysis of cell trajectories will identify key points of deviation from differentiation and predict mechanism leading to off-target cell-type generation. Aim 2: Develop 2D closed-loop CM differentiation processes and evaluate their robustness compared to standard protocols. We will build genetic and epigenetic sensor hPSC lines to monitor gene expression and chromatin accessibility at the single-cell level, test modulation of cardiac developmental pathways to rescue low efficiency CM batches, and compare the robustness of closed-loop processes to standard protocols. Aim 3: Develop scalable, 3D closed-loop CM differentiation processes and assess process variability. Utilizing a 3D bioreactors for CM manufacturing, we will compare failure modes in 3D to 2D differentiation, develop cell sensors and processes to modulate developmental signaling pathways, and increase the reliability of CM production in scalable manufacturing platforms.


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 = $578,478 )
2026	2026	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	001	2	3/25/2026	NON-COMPETING CONTINUATION	$17,709
2026	2026	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	2	2/20/2026	NON-COMPETING CONTINUATION	$560,769
														Subtotal = $578,478

Issue Date FY: 2025 ( Subtotal = $590,283 )
2025	2025	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6301	MADISON	WI	53715	DANE	USA	Cardiovascular Diseases Research	000	1	1/27/2025	NEW	$590,283
														Subtotal = $590,283

Grand Total All Awards = $1,168,761

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Technologies enabling robust closed-loop manufacturing of human pluripotent stem cell-derived cardiomyocytes

Award Number: R01HL178095

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/01/2025

PERIOD OF PERFORMANCE END DATE: 11/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer