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Updated: Dec 24, 2025
Capturing the Cardiac Injury Response of Targeted Cell Populations via Cleared Heart Three-Dimensional Imaging
Published on: March 17, 2020
Capturing the Cardiac Injury Response of Targeted Cell Populations via Cleared Heart Three-Dimensional Imaging
Rebecca J Salamon1, Ziheng Zhang1, Ahmed I Mahmoud2
1Department of Cell and Regenerative Biology, University of Wisconsin-Madison School of Medicine and Public Health.
Insights
Neonatal mice regenerate heart tissue after injury. Advanced 3D imaging and lineage tracing in a new myocardial infarction model reveal pathways for cardiac regeneration and potential therapeutic targets.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Developmental Biology
Background:
- Cardiovascular disease is a leading cause of death globally, often resulting in irreversible cardiac scarring and heart failure.
- Neonatal mice possess remarkable cardiac regenerative capabilities following injury, making them a valuable model organism.
- Traditional methods for studying cardiac injury lack the resolution and dimensionality to fully understand regenerative processes.
Purpose of the Study:
- To develop a clinically relevant model of myocardial infarction in neonatal mice.
- To utilize advanced imaging and lineage tracing techniques to investigate cardiac regeneration mechanisms.
- To identify novel therapeutic targets for promoting heart repair.
Main Methods:
- Development of a surgical procedure to induce left anterior descending artery (LAD) occlusion in neonatal mice, mimicking human myocardial infarction.
- Application of lineage tracing models, whole organ clearing, and 3D whole-mount microscopy for detailed cellular analysis.
- Integration of these techniques to track cellular changes and lineage in response to cardiac injury.
Main Results:
- The developed LAD occlusion model effectively replicates myocardial infarction in neonatal mice.
- Advanced 3D imaging and lineage tracing provide unprecedented insights into cardiomyocyte and non-myocyte population dynamics post-injury.
- The study successfully elucidates complex pathways driving cardiomyocyte proliferation and cardiac repair.
Conclusions:
- The neonatal mouse model combined with advanced 3D imaging and lineage tracing is a powerful platform for studying cardiac regeneration.
- Understanding the mechanisms of neonatal cardiac repair can reveal novel therapeutic strategies for treating heart failure in humans.
- This research paves the way for developing new treatments to enhance the heart's regenerative capacity.
Abstract:
Cardiovascular disease outranks all other causes of death and is responsible for a staggering 31% of mortalities worldwide. This disease manifests in cardiac injury, primarily in the form of an acute myocardial infarction. With little resilience following injury, the once healthy cardiac tissue will be replaced by fibrous, non-contractile scar tissue and often be a prelude to heart failure. To identify novel treatment options in regenerative medicine, research has focused on vertebrates with innate regenerative capabilities. One such model organism is the neonatal mouse, which responds to cardiac injury with robust myocardial regeneration. In order to induce an injury in the neonatal mouse that is clinically relevant, we have developed a surgery to occlude the left anterior descending artery (LAD), mirroring a myocardial infarction triggered by atherosclerosis in the human heart. When matched with the technology to track changes both within cardiomyocytes and non-myocyte populations, this model provides us with a platform to identify the mechanisms that guide heart regeneration. Gaining insight into changes in cardiac cell populations following injury once relied heavily on methods such as tissue sectioning and histological examination, which are limited to two-dimensional analysis and often damage the tissue in the process. Moreover, these methods lack the ability to trace changes in cell lineages, instead providing merely a snapshot of the injury response. Here, we describe how technologically advanced methods in lineage tracing models, whole organ clearing, and three-dimensional (3D) whole-mount microscopy can be used to elucidate mechanisms of cardiac repair. With our protocol for neonatal mouse myocardial infarction surgery, tissue clearing, and 3D whole organ imaging, the complex pathways that induce cardiomyocyte proliferation can be unraveled, revealing novel therapeutic targets for cardiac regeneration.
