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Human Engineered Heart Tissue Patches Remuscularize the Injured Heart in a Dose-Dependent Manner.
Eva Querdel1,2, Marina Reinsch1,2, Liesa Castro3,2,4
1Department of Experimental Pharmacology and Toxicology (E.Q., M.R., D.K., S.R., B.G., B.U., M.S., T.K., M.L., J.S., A.S., T.S., C.v.B., Y.N., I.M., T.C., A.H., T.E., F.W.), University Medical Center, Hamburg-Eppendorf, Germany.
Circulation
|March 2, 2021
Summary
Human engineered heart tissue (EHT) patches show promise for heart failure treatment, improving function in a dose-dependent manner. Human-scale patches were successfully transplanted in pigs, paving the way for clinical applications.
Area of Science:
- Regenerative Medicine
- Cardiovascular Biology
- Biotechnology
Background:
- Human engineered heart tissue (EHT) transplantation is a potential regenerative therapy for heart failure, proven effective in preclinical studies.
- Clinical translation requires upscaling EHT production under good manufacturing practices (GMP) and determining optimal therapeutic dosage.
- Current challenges include adapting protocols for large-scale GMP-compliant EHT generation and assessing efficacy in relevant models.
Purpose of the Study:
- To develop and evaluate human engineered heart tissue (EHT) patches for potential transplantation in heart failure patients.
- To adapt EHT generation protocols for good manufacturing practice (GMP) compliance and scale-up.
- To assess the efficacy and safety of EHT transplantation in preclinical models and evaluate human-scale patch feasibility.
Main Methods:
- Differentiated cardiomyocytes from GMP-grade human induced pluripotent stem cells (hiPSCs).
- Adapted protocols for hiPSC expansion, cardiomyocyte differentiation, and EHT generation using GMP-compliant materials.
- Created mesh-structured EHT patches of varying sizes for guinea pig and pig models, modifying geometry for transplantation.
Main Results:
- Generated EHT patches (1.5x2.5 cm for guinea pigs, 5x7 cm for pigs) with mature cardiomyocytes exhibiting human ventricular tissue characteristics.
- Transplanted EHT patches into cryo-injured guinea pig hearts, observing dose-dependent remuscularization (0-12% scar coverage).
- High-dose EHT patches significantly improved left ventricular function (+8% absolute, +24% relative) and demonstrated cardiomyocyte proliferation; human-scale patches were successfully transplanted in pigs.
Conclusions:
- EHT patch transplantation partially remuscularized injured hearts and improved left ventricular function in a dose-dependent manner in guinea pigs.
- Human-scale EHT patches were successfully transplanted in pigs, demonstrating proof-of-principle for clinical feasibility.
- These findings support the advancement of EHT transplantation as a viable regenerative strategy for heart failure.
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