Living myocardial slices: walking the path towards standardization

Area of Science:

• Cardiovascular Research
• Pre-clinical Drug Development
• Tissue Engineering

Background:

• Cardiovascular diseases, particularly heart failure, present a significant global health challenge.
• Current pre-clinical models have limitations in accurately recapitulating human heart complexity, leading to high drug development attrition rates.
• Living myocardial slices (LMS) are emerging as a valuable ex vivo model due to their native architecture and potential for extended culture.

Purpose of the Study:

• To review and highlight variability in current living myocardial slices (LMS) methodologies.
• To provide guidelines for standardization to enhance reproducibility and comparability in LMS research.
• To strengthen the role of LMS in cardiovascular research and drug development.

Main Methods:

• Comprehensive review of sample selection, interspecies and intra-cardiac variations, and confounding factors.
• Examination of diverse culture methods, including electrical and mechanical stimulation and medium compositions.
• Analysis of current limitations and identification of areas for standardization in LMS research.

Main Results:

• Significant variability exists in LMS preparation and culture methodologies across studies.
• Differences in sample handling, stimulation, and media impact LMS experimental outcomes.
• Lack of standardization hinders reproducibility and direct comparison of LMS research findings.

Conclusions:

• Standardization of LMS methodologies is essential for advancing cardiovascular research and drug discovery.
• Clear reporting of experimental details is critical for reproducibility and validation of LMS models.
• LMS represent a powerful tool, but require methodological refinement to maximize their potential in pre-clinical studies.