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Large Animal Models of Heart Failure: A Translational Bridge to Clinical Success.

ABSTRACT: Preclinical large animal models of heart failure (HF) play a critical and expanding role in translating basic science findings to the development and clinical approval of novel therapeutics and devices. The complex combination of cardiovascular events and risk factors leading to HF has proved challenging for the development of new treatments for these patients. This state-of-the-art review presents historical and recent studies in porcine, ovine, and canine models of HF and outlines existing methodologies and physiological phenotypes. The translational importance of large animal studies to clinical success is also highlighted with an overview of recent devices approved by the Food and Drug Administration, together with preclinical HF animal studies used to aid both development and safety and/or efficacy testing. Increasing the use of large animal models of HF holds significant potential for identifying the novel mechanisms underlying the clinical condition and to improving physiological and economical translation of animal research to successfully treat human HF.

SUBMITTER: Silva KAS

PROVIDER: S-EPMC7452204 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Large Animal Models of Heart Failure: A Translational Bridge to Clinical Success.

Silva Kleiton Augusto Santos KAS Emter Craig A CA

JACC. Basic to translational science 20200824 8

Preclinical large animal models of heart failure (HF) play a critical and expanding role in translating basic science findings to the development and clinical approval of novel therapeutics and devices. The complex combination of cardiovascular events and risk factors leading to HF has proved challenging for the development of new treatments for these patients. This state-of-the-art review presents historical and recent studies in porcine, ovine, and canine models of HF and outlines existing met ...[more]

PMID: 32875172

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Project description:Animal organoid models derived from farm and companion animals have great potential to contribute to human health as a One Health initiative, which recognize a close inter-relationship among humans, animals and their shared environment and adopt multi-and trans-disciplinary approaches to optimize health outcomes. With recent advances in organoid technology, studies on farm and companion animal organoids have gained more attention in various fields including veterinary medicine, translational medicine and biomedical research. Not only is this because three-dimensional organoids possess unique characteristics from traditional two-dimensional cell cultures including their self-organizing and self-renewing properties and high structural and functional similarities to the originating tissue, but also because relative to conventional genetically modified or artificially induced murine models, companion animal organoids can provide an excellent model for spontaneously occurring diseases which resemble human diseases. These features of companion animal organoids offer a paradigm-shifting approach in biomedical research and improve translatability of in vitro studies to subsequent in vivo studies with spontaneously diseased animals while reducing the use of conventional animal models prior to human clinical trials. Farm animal organoids also could play an important role in investigations of the pathophysiology of zoonotic and reproductive diseases by contributing to public health and improving agricultural production. Here, we discuss a brief history of organoids and the most recent updates on farm and companion animal organoids, followed by discussion on their potential in public health, food security, and comparative medicine as One Health initiatives. We highlight recent evolution in the culturing of organoids and their integration with organ-on-a-chip systems to overcome current limitations in in vitro studies. We envision multidisciplinary work integrating organoid culture and organ-on-a-chip technology can contribute to improving both human and animal health.

Project description:The Sydney Heart Bank (SHB) is one of the largest human heart tissue banks in existence. Its mission is to provide high-quality human heart tissue for research into the molecular basis of human heart failure by working collaboratively with experts in this field. We argue that, by comparing tissues from failing human hearts with age-matched non-failing healthy donor hearts, the results will be more relevant than research using animal models, particularly if their physiology is very different from humans. Tissue from heart surgery must generally be used soon after collection or it significantly deteriorates. Freezing is an option but it raises concerns that freezing causes substantial damage at the cellular and molecular level. The SHB contains failing samples from heart transplant patients and others who provided informed consent for the use of their tissue for research. All samples are cryopreserved in liquid nitrogen within 40 min of their removal from the patient, and in less than 5-10 min in the case of coronary arteries and left ventricle samples. To date, the SHB has collected tissue from about 450 failing hearts (>15,000 samples) from patients with a wide range of etiologies as well as increasing numbers of cardiomyectomy samples from patients with hypertrophic cardiomyopathy. The Bank also has hearts from over 120 healthy organ donors whose hearts, for a variety of reasons (mainly tissue-type incompatibility with waiting heart transplant recipients), could not be used for transplantation. Donor hearts were collected by the St Vincent's Hospital Heart and Lung transplantation team from local hospitals or within a 4-h jet flight from Sydney. They were flushed with chilled cardioplegic solution and transported to Sydney where they were quickly cryopreserved in small samples. Failing and/or donor samples have been used by more than 60 research teams around the world, and have resulted in more than 100 research papers. The tissues most commonly requested are from donor left ventricles, but right ventricles, atria, interventricular system, and coronary arteries vessels have also been reported. All tissues are stored for long-term use in liquid N or vapor (170-180 °C), and are shipped under nitrogen vapor to avoid degradation of sensitive molecules such as RNAs and giant proteins. We present evidence that the availability of these human heart samples has contributed to a reduction in the use of animal models of human heart failure.

Dataset Information

Large Animal Models of Heart Failure: A Translational Bridge to Clinical Success.

Publications

Large Animal Models of Heart Failure: A Translational Bridge to Clinical Success.

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