Engineered Heart Tissue Models for Neurological Disease Cardiac Comorbidities
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Solution Overview
Problem
Current models for studying cardiac effects in patients with neurological diseases, such as Friedreich's ataxia, are inadequate due to limited availability of patient biopsies and inability to recapitulate functional phenotypes like contractile dysfunction.
Innovation Solution
The development of engineered human heart tissue models using human induced pluripotent stem cells (hiPSCs) that can be differentiated into cardiomyocytes, allowing for the creation of cardiac anisotropic sheets, tissue strips, and organoid chambers to model cardiac electrophysiology and contractility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If patient biopsies are used to study cardiac effects, then the model reflects actual patient pathology, but the availability is limited and the tissue is inadequate for recapitulating functional phenotypes
Solution Approach 1:
The patent creates in vitro copies of patient-specific cardiac tissue using hiPSCs derived from patients with neurological diseases. These engineered heart tissues replicate the genetic and phenotypic characteristics of patient cardiomyocytes, enabling study of disease-specific cardiac effects without requiring actual patient biopsies. The copying approach allows unlimited propagation of disease-specific cellular models.
Solution Approach 2:
The patent transforms the biological state of cells by reprogramming somatic cells into induced pluripotent stem cells, then differentiating them into cardiomyocytes. This parameter change in cellular identity and function enables the creation of functional cardiac tissue models from non-cardiac patient cells, overcoming the limitation of tissue availability while maintaining disease-specific characteristics.
2Productivity
If single-cell properties are measured, then the data is easy to obtain, but the properties are difficult to extrapolate into tissue-level phenotypes
Solution Approach 1:
The patent transitions from studying isolated single cells to engineered three-dimensional heart tissue constructs. This dimensional escalation allows the system to capture tissue-level phenomena such as synchronous contraction, electrical conduction, and mechanical coupling that cannot be observed or extrapolated from single-cell measurements alone.
Solution Approach 2:
The patent creates composite engineered heart tissues by combining patient-specific cardiomyocytes with supportive cell types and extracellular matrix components. This composite structure recapitulates the complexity of native cardiac tissue, enabling measurement of emergent tissue-level properties that arise from cellular interactions rather than individual cell behavior.
3Ease of manufacture
If traditional monolayer cultures are used, then the setup is simple, but they do not recapitulate the anisotropic three-dimensional structure and function of heart tissue
Solution Approach 1:
The patent advances from two-dimensional monolayer cultures to three-dimensional engineered heart tissue constructs. This dimensional transition enables recapitulation of the anisotropic structural organization and functional properties of native cardiac tissue, including directional muscle fiber arrangement and coordinated contraction patterns that are absent in flat monolayers.
Data Source
AI summary
A system for screening compounds for therapeutic cardiac effects in the cells, tissues and organoids (1) of patients having diseases such as neurological diseases or disorders with significant cardiac comorbidities. The system comprises a medical device apparatus that can be suitable for a single-tier screen for cardio-active compounds that comprises a human ventricular cardiac anisotropic sheet (hvCAS) and human ventricular cardiac tissue strip (hvCTS), a two-tier system further comprising human ventricular cardiac organoid chamber (hvCOC) (20), or a three-tier system still further comprising a medical device comprising multiple organoids (20), which include tissues or organoids (1) of the same or different type (e.g., heart, liver, pancreas, kidney). Another aspect of the disclosure is the methods suitable for use with the systems, comprising screens for identifying compounds having cardiac effects on cells, tissues or organoids (1) of patients having a non-cardiac disease exhibiting a cardiac effect, such as neurological diseases. The methods are further useful in assessing the toxicity of compounds to various cells, tissues or organoids (1) of such patients.