Large animal models for cardiac remuscularization studies: A methodological review

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...

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Main Authors: Yuexin Yu, Seng Kong Tham, Fatin Fazrina Roslan, Bakiah Shaharuddin, Yoke Keong Yong, Zhikun Guo, Jun Jie Tan
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Cardiovascular Medicine
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2023.1011880/full
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author Yuexin Yu
Yuexin Yu
Yuexin Yu
Seng Kong Tham
Fatin Fazrina Roslan
Bakiah Shaharuddin
Yoke Keong Yong
Zhikun Guo
Zhikun Guo
Jun Jie Tan
author_facet Yuexin Yu
Yuexin Yu
Yuexin Yu
Seng Kong Tham
Fatin Fazrina Roslan
Bakiah Shaharuddin
Yoke Keong Yong
Zhikun Guo
Zhikun Guo
Jun Jie Tan
author_sort Yuexin Yu
collection DOAJ
description 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.
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spelling doaj.art-b2346091551d40dd9035bd50291bbbf02023-03-15T05:47:52ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-03-011010.3389/fcvm.2023.10118801011880Large animal models for cardiac remuscularization studies: A methodological reviewYuexin Yu0Yuexin Yu1Yuexin Yu2Seng Kong Tham3Fatin Fazrina Roslan4Bakiah Shaharuddin5Yoke Keong Yong6Zhikun Guo7Zhikun Guo8Jun Jie Tan9USM-ALPS Cardiac Research Laboratory, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, MalaysiaHenan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, ChinaHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, ChinaCelestialab Sdn Bhd, Kuala Lumpur, MalaysiaUSM-ALPS Cardiac Research Laboratory, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, MalaysiaUSM-ALPS Cardiac Research Laboratory, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, MalaysiaDepartment of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, MalaysiaHenan Key Laboratory of Cardiac Remodeling and Transplantation, Zhengzhou Seventh People's Hospital, ChinaHenan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, ChinaUSM-ALPS Cardiac Research Laboratory, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Penang, MalaysiaMyocardial 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.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1011880/fullcardiac regenerationlarge animal modelspluripotent stem cells (PSC)cardiomyocytescardiac remuscularizationmyocardial infarction
spellingShingle Yuexin Yu
Yuexin Yu
Yuexin Yu
Seng Kong Tham
Fatin Fazrina Roslan
Bakiah Shaharuddin
Yoke Keong Yong
Zhikun Guo
Zhikun Guo
Jun Jie Tan
Large animal models for cardiac remuscularization studies: A methodological review
Frontiers in Cardiovascular Medicine
cardiac regeneration
large animal models
pluripotent stem cells (PSC)
cardiomyocytes
cardiac remuscularization
myocardial infarction
title Large animal models for cardiac remuscularization studies: A methodological review
title_full Large animal models for cardiac remuscularization studies: A methodological review
title_fullStr Large animal models for cardiac remuscularization studies: A methodological review
title_full_unstemmed Large animal models for cardiac remuscularization studies: A methodological review
title_short Large animal models for cardiac remuscularization studies: A methodological review
title_sort large animal models for cardiac remuscularization studies a methodological review
topic cardiac regeneration
large animal models
pluripotent stem cells (PSC)
cardiomyocytes
cardiac remuscularization
myocardial infarction
url https://www.frontiersin.org/articles/10.3389/fcvm.2023.1011880/full
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