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Published on: June 16, 2022
Large animal models for cardiac remuscularization studies: A methodological review
Yuexin Yu1,2,3, Seng Kong Tham4, Fatin Fazrina Roslan1
1USM-ALPS Cardiac Research Laboratory, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, Malaysia.
Insights
Large animal models are crucial for testing the efficacy and safety of cardiomyocyte therapy for heart attack (myocardial infarction) regeneration before human trials. This review details methods for these vital preclinical studies.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Stem Cell Therapy
Background:
- Myocardial infarction (MI) is a leading cause of heart failure and mortality.
- Regenerating dead heart tissue with functional cardiomyocytes offers a potential therapeutic strategy.
- Human pluripotent stem cell-derived cardiomyocytes show promise for cardiac repair.
Purpose of the Study:
- To review large animal models for testing cardiomyocyte therapy in myocardial infarction.
- To assess the translatability of preclinical findings to clinical practice.
- To discuss methodologies for simulating human MI pathophysiology in animal models.
Main Methods:
- Focus on large mammal models simulating human myocardial infarction.
- Discussion of MI induction methodologies and animal species selection.
- Review of perioperative care, immunosuppression for xenotransplantation, cell source, and delivery.
Main Results:
- Large animal models are essential for rigorous safety and efficacy testing of stem cell-based cardiac remuscularization.
- Preclinical studies in large mammals increase the likelihood of successful clinical translation.
- Various aspects of model development and therapeutic delivery are critical for success.
Conclusions:
- Large animal models are indispensable for advancing cardiomyocyte therapy for myocardial infarction.
- Standardized methodologies in these models are key for reliable preclinical data.
- This review provides a framework for future research in cardiac regenerative medicine.
Abstract:
Myocardial infarction is the most common cause of heart failure, one of the most fatal non-communicable diseases worldwide. The disease could potentially be treated if the dead, ischemic heart tissues are regenerated and replaced with viable and functional cardiomyocytes. Pluripotent stem cells have proven the ability to derive specific and functional cardiomyocytes in large quantities for therapy. To test the remuscularization hypothesis, the strategy to model the disease in animals must resemble the pathophysiological conditions of myocardial infarction as in humans, to enable thorough testing of the safety and efficacy of the cardiomyocyte therapy before embarking on human trials. Rigorous experiments and in vivo findings using large mammals are increasingly important to simulate clinical reality and increase translatability into clinical practice. Hence, this review focus on large animal models which have been used in cardiac remuscularization studies using cardiomyocytes derived from human pluripotent stem cells. The commonly used methodologies in developing the myocardial infarction model, the choice of animal species, the pre-operative antiarrhythmics prophylaxis, the choice of perioperative sedative, anaesthesia and analgesia, the immunosuppressive strategies in allowing xenotransplantation, the source of cells, number and delivery method are discussed.
