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The Current State of Realistic Heart Models for Disease Modelling and Cardiotoxicity
Kornél Kistamás1, Federica Lamberto1,2, Raminta Vaiciuleviciute3
1BioTalentum Ltd., Aulich Lajos Str 26, H-2100 Gödöllő, Hungary.
Insights
Developing mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is crucial for realistic cardiovascular disease modeling. This review covers advanced techniques to improve hiPSC-CMs for better drug development and toxicity testing.
Area of Science:
- Cardiovascular Research
- Stem Cell Biology
- Biomedical Engineering
Background:
- Establishing reliable in vitro cardiac models is a persistent challenge in cardiovascular research.
- Ethical and legal issues limit the use of human primary cardiomyocytes, while animal models have drawbacks.
- Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) offer a scalable source but require maturation for physiological relevance.
Purpose of the Study:
- To review current state-of-the-art techniques for maturing hiPSC-CMs.
- To explore advanced in vitro cardiac models for disease and toxicity evaluation.
- To address the bottleneck of achieving adult-like maturity in hiPSC-CMs.
Main Methods:
- Review of literature on hiPSC-CM maturation techniques.
- Analysis of heart-on-a-chip platforms for advanced modeling.
- Inclusion of in silico models and specific cardiovascular disease in vitro models.
Main Results:
- hiPSC-CMs represent a promising, abundant source for cardiac research.
- Significant progress has been made in maturing hiPSC-CMs towards adult-like phenotypes.
- Integrated approaches combining hiPSC-CMs with advanced platforms enhance model realism.
Conclusions:
- Maturation of hiPSC-CMs is key to overcoming limitations in current cardiac models.
- Advanced techniques like heart-on-a-chip and in silico models improve disease modeling and drug testing.
- Achieving mature hiPSC-CMs is essential for accurate cardiovascular research and drug development.
Abstract:
One of the many unresolved obstacles in the field of cardiovascular research is an uncompromising in vitro cardiac model. While primary cell sources from animal models offer both advantages and disadvantages, efforts over the past half-century have aimed to reduce their use. Additionally, obtaining a sufficient quantity of human primary cardiomyocytes faces ethical and legal challenges. As the practically unlimited source of human cardiomyocytes from induced pluripotent stem cells (hiPSC-CM) is now mostly resolved, there are great efforts to improve their quality and applicability by overcoming their intrinsic limitations. The greatest bottleneck in the field is the in vitro ageing of hiPSC-CMs to reach a maturity status that closely resembles that of the adult heart, thereby allowing for more appropriate drug developmental procedures as there is a clear correlation between ageing and developing cardiovascular diseases. Here, we review the current state-of-the-art techniques in the most realistic heart models used in disease modelling and toxicity evaluations from hiPSC-CM maturation through heart-on-a-chip platforms and in silico models to the in vitro models of certain cardiovascular diseases.
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