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In vitro models of the cardiac microenvironment to study myocyte and non-myocyte crosstalk: bioinspired approaches
Celinda M Kofron1, Ulrike Mende1
1Cardiovascular Research Center, Cardiovascular Institute, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, RI, USA.
Insights
Heart cells, including myocytes and non-myocytes, communicate dynamically. Understanding this crosstalk is key for developing better in vitro models for heart disease research and drug testing.
Area of Science:
- Cardiovascular Biology
- Cellular and Molecular Medicine
- Biomedical Engineering
Background:
- The heart comprises cardiomyocytes and non-myocytes (fibroblasts, endothelial, immune cells) with crucial intercellular communication.
- Myocyte-non-myocyte crosstalk regulates myocardial structure, electrical properties, and mechanical function in health and disease.
- This communication is vital in pathological conditions like cardiac hypertrophy, fibrosis, heart failure, and arrhythmias.
Purpose of the Study:
- To highlight the importance of myocyte-non-myocyte communication in cardiac function and disease.
- To discuss the limitations of current in vitro models in replicating the complex cardiac microenvironment.
- To emphasize the need for advanced pluricellular platforms for physiologically relevant cardiac research.
Main Methods:
- Review of existing literature on cardiac cell communication and in vitro modeling.
- Analysis of the role of heterocellular interactions in myocardial remodeling and heart failure.
- Discussion of the challenges in studying cardiac cell crosstalk within complex tissue architecture.
Main Results:
- Dynamic crosstalk between cardiac cell types is essential for maintaining myocardial homeostasis and response to stress.
- Current in vitro models often fail to capture the full complexity of the cardiac microenvironment, limiting their physiological relevance.
- Advanced pluricellular platforms are needed to better mimic in vivo conditions.
Conclusions:
- Understanding cardiac cell communication is critical for advancing heart disease research.
- Development of sophisticated in vitro cardiac models is crucial for accurate disease modeling, drug testing, and regenerative medicine.
- Future research should focus on creating more physiologically relevant cardiac tissue models that incorporate diverse microenvironmental cues.
Abstract:
The heart is a complex pluricellular organ composed of cardiomyocytes and non-myocytes including fibroblasts, endothelial cells and immune cells. Myocytes are responsible for electrical conduction and contractile force generation, while the other cell types are responsible for matrix deposition, vascularization, and injury response. Myocytes and non-myocytes are known to communicate and exert mutual regulatory effects. In concert, they determine the structural, electrical and mechanical characteristics in the healthy and remodelled myocardium. Dynamic crosstalk between myocytes and non-myocytes plays a crucial role in stress/injury-induced hypertrophy and fibrosis development that can ultimately lead to heart failure and arrhythmias. Investigations of heterocellular communication in the myocardium are hampered by the intricate interspersion of the different cell types and the complexity of the tissue architecture. In vitro models have facilitated investigations of cardiac cells in a direct and controllable manner and have provided important functional and mechanistic insights. However, these cultures often lack regulatory input from the other cell types as well as additional topographical, electrical, mechanical and biochemical cues from the cardiac microenvironment that all contribute to modulating cell differentiation, maturation, alignment, function and survival. Advancements in the development of more complex pluricellular physiological platforms that incorporate diverse cues from the myocardial microenvironment are expected to lead to more physiologically relevant cardiac tissue-like in vitro models for mechanistic biological research, disease modelling, therapeutic target identification, drug testing and regeneration.
