Multi-Compartment Heart Tissue Fusion With Shared Chambers
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Solution Overview
Problem
Current human heart tissue models fail to accurately represent the diversity and complexity of developing heart compartments, such as the outflow tract, atria, right ventricle, and left ventricle, due to species-specific physiological differences and limited mechanistic dissection capabilities.
Innovation Solution
A heart tissue model comprising multiple heart tissues with shared inner cavities and calcium signaling connections, allowing for the propagation of tissue contractions, is generated by fusing progenitor heart field tissues in vitro, using controlled developmental signaling pathways.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If self-organizing cardiac organoid models are used, then accessibility and high throughput statistical significance capability are improved, but the ability to model all interacting compartments of the human embryonic heart is insufficient
Solution Approach 1:
The invention segments the heart development process into distinct compartment-specific organoid models (OFT, AVC, atria, RV, LV) that can be independently generated and then combined. Each organoid type focuses on a specific heart compartment, allowing for specialized modeling while maintaining the overall capability to represent the complete heart through combinations of these segmented models.
Solution Approach 2:
The invention merges multiple compartment-specific organoid models into integrated systems that can represent all interacting compartments of the human embryonic heart. By combining OFT, AVC, atria, RV, and LV organoids, the system achieves comprehensive modeling capability while retaining the productivity benefits of individual specialized models.
2Measurement precision
If animal models are used to study heart defects, then mechanistic dissection is possible, but complexity, speed, inaccessibility and species-specific physiological differences create challenges
Solution Approach 1:
The invention creates simplified copies of human heart compartments using organoid models derived from human pluripotent stem cells. These organoid copies capture the essential mechanistic features of each heart compartment (OFT, AVC, atria, RV, LV) without the complexity of whole animal systems, while maintaining human-specific physiology through the use of human cellular sources.
3Ease of manufacture
If conventional artificial heart tissue models are used, then ease of manufacture is improved, but the diversity of in vivo heart development is not represented
Solution Approach 1:
The invention applies local quality by optimizing each organoid model for its specific heart compartment function. Each compartment (OFT, AVC, atria, RV, LV) is modeled with appropriate cellular compositions, signaling environments, and structural characteristics specific to that region, while maintaining relatively simple manufacturing protocols that build upon conventional organoid generation methods.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The model recapitulates the functional diversity of human heart compartments, enabling advanced mechanistic studies and screenings for heart development and injury treatments.
Implementation Method 1
self-organization after initiation of cardiac differentiation using specific drifting factors
Implementation Method 2
the at least two different heart tissues comprise a calcium signaling connection and/or ability to propagate a tissue contraction
Data Source
AI summary
A heart tissue model including a heart tissue with at least one inner cavity or a central chamber, wherein the heart tissue model including at least two different heart tissues selected from left ventricle tissue, right ventricle tissue, atrial tissue, outflow tract tissue, atrioventricular canal tissue, sinoatrial node tissue, and atrioventricular node tissue, wherein the central chamber can be shared by at least two different heart tissues, and wherein the at least two different heart tissues include a calcium signaling connection and/or ability to propagate a tissue contraction-; methods of generating such a tissue model and uses of the tissue model for screening purposes is disclosed.