Animal Disease Models and Patient-iPS Cell Derived In Vitro Disease Models for Cardiovascular Biology—How Close to Disease?

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 4061

Special Issue Editors


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Guest Editor
Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
Interests: stem cells; chemokines; macrophagse; CXCR4; SDF-1; iPS cells
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women’s Medical University, Tokyo 162-8666, Japan
Interests: stem cell; regeneration
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Currently, murines, rodents, canines, and pigs are used as disease models in cardiovascular research. Larger animals that are more closely related to humans make better-suited disease models. However, they can have restricted or limited use, as they are difficult to handle and maintain. Moreover, experimental animals are regulated by animal welfare policies. Different species have different internal disease onset mechanisms. Nonetheless, preclinical studies use animals to check the safety and efficacy of human drugs because no other complementary method exists. Hence, we need to evaluate the similarities and differences in the disease mechanisms between humans and experimental animals. Humanized or chimerically humanized animal models can be used to more closely imitate human systems, especially when stem cells are involved. Humanized animal models use immuno-deficient mice and transplant human disease cells, such as cancer cells. In cardiovascular disease research, bone marrow stem cells (BMSCs) have been studied to treat myocardial infarction (MI). For this purpose, human BMSCs were injected into a humanized chimeric mouse with irradiated bone marrow.

Human cardiac cells, such as cardiomyocytes have been generated from patient-derived induced pluripotent stem cells (iPSCs) since iPSCs were first discovered. The patient-derived iPSCs and the cardiac cells were genetically equal to those that derived from the patient. However, variations in human iPSCs (hiPSCs) and hiPSCs-derived cardiomyocytes (hiPSCs-CMs) make it difficult to analyze disease-specific differences. Researchers have tried to develop 3D-culture systems that mimic in vivo conditions using various iPSC-derived cardiac cells to overcome this issue.

In this Special Issue, we would like to explore the possibility of animal disease models and iPSC-derived in vitro disease models.

Dr. Nanako Kawaguchi
Dr. Toshio Nakanishi
Guest Editors

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Keywords

  • animal disease model
  • iPS cells
  • transgenic
  • mutation
  • stem cells
  • in vitro
  • in vivo
  • patient-derived iPSCs

Published Papers (2 papers)

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15 pages, 19584 KiB  
Article
Ability of the Right Ventricle to Serve as a Systemic Ventricle in Response to the Volume Overload at the Neonatal Stage
by Chunxia Zhou, Debao Li, Qing Cui, Qi Sun, Yuqing Hu, Yingying Xiao, Chuan Jiang, Lisheng Qiu, Haibo Zhang, Lincai Ye and Yanjun Sun
Biology 2022, 11(12), 1831; https://doi.org/10.3390/biology11121831 - 15 Dec 2022
Cited by 2 | Viewed by 1310
Abstract
Background: In children with hypoplastic left heart syndrome (HLHS), volume overload (VO) is inevitable, and the right ventricle (RV) pumps blood into the systemic circulation. Understanding the molecular differences and their different responses to VO between the RV and left ventricle (LV) at [...] Read more.
Background: In children with hypoplastic left heart syndrome (HLHS), volume overload (VO) is inevitable, and the right ventricle (RV) pumps blood into the systemic circulation. Understanding the molecular differences and their different responses to VO between the RV and left ventricle (LV) at the neonatal and highly plastic stages may improve the long-term management of children with HLHS. Methods and Results: A neonatal rat ventricular VO model was established by the creation of a fistula between the inferior vena cava and the abdominal aorta on postnatal day 1 (P1) and confirmed by echocardiographic and histopathological analyses. Transcriptomic analysis demonstrated that some of the major differences between a normal neonatal RV and LV were associated with the thyroid hormone and insulin signaling pathways. Under the influence of VO, the levels of insulin receptors and thyroid hormone receptors were significantly increased in the LV but decreased in the RV. The transcriptomic analysis also demonstrated that under the influence of VO, the top two common enriched pathways between the RV and LV were the insulin and thyroid hormone signaling pathways, whereas the RV-specific enriched pathways were primarily associated with lipid metabolism and arrhythmogenic right ventricular cardiomyopathy (ARVC); further, the LV-specific enriched pathways were primarily associated with nucleic acid metabolism and microRNAs in cancer. Conclusions: Insulin and thyroid hormones may play critical roles in the differences between a neonatal RV and LV as well as their common responses to VO. Regarding the isolated responses to VO, the RV favors an ARVC change and the LV favors a reduction in microRNAs in cancer. The current study suggests that insulin, thyroid hormone, and cancer-associated microRNAs are potential therapeutic targets that should be explored by basic science studies to improve the function of the RV to match that of the LV. Full article
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Review

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14 pages, 998 KiB  
Review
Animal Disease Models and Patient-iPS-Cell-Derived In Vitro Disease Models for Cardiovascular Biology—How Close to Disease?
by Nanako Kawaguchi and Toshio Nakanishi
Biology 2023, 12(3), 468; https://doi.org/10.3390/biology12030468 - 20 Mar 2023
Cited by 2 | Viewed by 2257
Abstract
Currently, zebrafish, rodents, canines, and pigs are the primary disease models used in cardiovascular research. In general, larger animals have more physiological similarities to humans, making better disease models. However, they can have restricted or limited use because they are difficult to handle [...] Read more.
Currently, zebrafish, rodents, canines, and pigs are the primary disease models used in cardiovascular research. In general, larger animals have more physiological similarities to humans, making better disease models. However, they can have restricted or limited use because they are difficult to handle and maintain. Moreover, animal welfare laws regulate the use of experimental animals. Different species have different mechanisms of disease onset. Organs in each animal species have different characteristics depending on their evolutionary history and living environment. For example, mice have higher heart rates than humans. Nonetheless, preclinical studies have used animals to evaluate the safety and efficacy of human drugs because no other complementary method exists. Hence, we need to evaluate the similarities and differences in disease mechanisms between humans and experimental animals. The translation of animal data to humans contributes to eliminating the gap between these two. In vitro disease models have been used as another alternative for human disease models since the discovery of induced pluripotent stem cells (iPSCs). Human cardiomyocytes have been generated from patient-derived iPSCs, which are genetically identical to the derived patients. Researchers have attempted to develop in vivo mimicking 3D culture systems. In this review, we explore the possible uses of animal disease models, iPSC-derived in vitro disease models, humanized animals, and the recent challenges of machine learning. The combination of these methods will make disease models more similar to human disease. Full article
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