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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.

Frontiers in Cardiovascular Medicine
|April 3, 2023
PubMed
Summary

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.

Keywords:
cardiac regenerationcardiac remuscularizationcardiomyocyteslarge animal modelsmyocardial infarctionpluripotent stem cells (PSC)

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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.