WITHDRAWN: Cell based dATP delivery as a therapy for chronic heart failure.
Biorxiv : the Preprint Server for Biology
|May 10, 2023
Summary
Engineered stem cell-derived cardiomyocytes (hPSC-CMs) that produce 2'-deoxy-ATP (dATP) improved heart function in chronic heart failure. This novel cell therapy approach enhanced host contractility and survival, offering new hope for treating failing hearts.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) show promise for acute myocardial infarction but are ineffective in chronic heart failure.
- Existing therapies for chronic heart failure have limited efficacy in restoring cardiac function.
Purpose of the Study:
- To engineer hPSC-CMs to enhance cardiac contractility and improve function in chronic heart failure models.
- To investigate the therapeutic potential of dATP-producing hPSC-CMs in a preclinical model of chronic myocardial infarction.
Main Methods:
- Engineered hPSC-CMs to overexpress ribonucleotide reductase for increased 2 -deoxy-ATP (dATP) production.
- Transplanted engineered hPSC-CMs into chronically infarcted hearts in vivo.
- Assessed graft integration, dATP transfer, cardiac function, exercise capacity, metabolism, and survival.
Main Results:
- dATP-producing hPSC-CM grafts formed new myocardium and increased host cardiomyocyte dATP levels via gap junctions.
- Transplantation of dATP-producing grafts significantly improved left ventricular function in chronic heart failure.
- Recipients showed enhanced exercise tolerance, improved cardiac metabolism, reduced congestion, and increased survival compared to controls.
Conclusions:
- Engineered dATP-producing hPSC-CMs offer a novel cell therapy for chronic heart failure by combining remuscularization with enhanced host contractility.
- This approach represents a promising strategy to treat the failing heart, addressing limitations of current stem cell therapies.
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