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From cells to systems: A comprehensive perspective on In-Vitro, In-Vivo, and 3D culture models of heart failure
Kushal Vesmaker1, Jegadheeswari Venkadakrishnan1, Arti Dhar1
1Department of Pharmacy, Birla Institute of Technology and Sciences (BITS) Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet, Hyderabad, Telangana, 500078, India.
Insights
Heart failure (HF) drug discovery faces challenges. This review examines in-vivo animal models, 2D cell cultures, and advanced 3D in-vitro models to improve therapeutic development for this cardiovascular condition.
Area of Science:
- Cardiovascular Research
- Drug Discovery and Development
- Biomedical Engineering
Background:
- Heart failure (HF) is a progressive cardiovascular disease with increasing global prevalence and high mortality rates.
- Current understanding of HF pathophysiology is advancing, yet effective therapeutic strategies remain elusive.
- Preclinical drug testing for HF relies on in-vitro and in-vivo models, each with limitations in accurately replicating disease complexity.
Purpose of the Study:
- To review current in-vitro and in-vivo models used for heart failure research and drug testing.
- To highlight the advantages and limitations of animal models, 2D cell cultures, and emerging 3D in-vitro models.
- To discuss the potential of advanced models in streamlining the heart failure drug discovery process.
Main Methods:
- Review of existing literature on in-vivo murine models of heart failure.
- Analysis of 2D cell culture systems for studying cellular responses in HF.
- Exploration of 3D in-vitro models as physiologically relevant platforms for HF research.
Main Results:
- In-vivo murine models offer insights into HF mechanisms but face translational challenges due to species-specific differences.
- 2D cell cultures provide controlled environments but lack the complexity of in-vivo cardiac tissue.
- 3D in-vitro models show promise in replicating the in-vivo cardiac milieu for more accurate preclinical drug testing.
Conclusions:
- A combination of in-vitro and in-vivo approaches is essential for comprehensive HF drug development.
- 3D in-vitro models represent a significant advancement, offering a more accurate preclinical testing platform.
- Optimizing HF models is critical for accelerating the translation of research findings into effective patient therapies.
Abstract:
Heart failure (HF) is a cardiovascular condition with varying etiology, in which the heart ceases to pump sufficient blood to the body. It is a major cause of death worldwide, with prevalence increasing continuously over the years. Despite tremendous progress in understanding HF pathophysiology, creating effective therapy strategies remains challenging, with high mortality rates and translating experimental findings into an effective therapeutic. Drug testing for HF utilizes in-vitro and in-vivo models to examine prospective treatments as well as therapeutic efficacy. In-vivo murine models of HF are frequently employed to recreate human disease phenotypes and identify their underlying mechanisms. It has significantly improved our understanding of the mechanisms underlying HF, paving the way for successful treatments. These models provide numerous information about cardiac functionality, but species-specific genetic differences may restrict their translational utility. In-vitro models, such as 2D cell cultures, offer a controlled environment for studying cellular responses to therapeutic interventions. However, standard 2D cultures fail to reproduce the 3D architecture and the cell-cell interaction in complex organ-level systems. Introducing 3D in-vitro models provides a physiologically realistic platform for an accurate replication of the in-vivo cardiac milieu, which is critical for accurate preclinical drug testing. Combining in-vitro and in-vivo techniques is crucial for developing HF therapeutics, as each model carries intrinsic advantages and limitations in representing the complexity of the disease. This review focuses on in-vitro and in-vivo HF models, highlighting animal models, 2D cultures, and emerging trends in 3D in-vitro models, offering potential for streamlining the drug discovery process.

