Large animal models for translational research in acute kidney injury

AbstractBackgroundLarge animal models, such as the dog, are increasingly being used over rodent models for studying naturally occurring diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between currently used animal models (e.g. mouse) and humans, and expand the translational potential of the dog model, we developed a three dimensional (3D) canine GI organoid (enteroid and colonoid) system. Organoids have recently gained interest in translational research as this model system better recapitulates the physiological and molecular features of the tissue environment in comparison with two-dimensional cultures.ResultsOrganoids were propagated from isolation of adult intestinal stem cells (ISC) from whole jejunal tissue as well as endoscopically obtained duodenal, ileal and colonic biopsy samples of healthy dogs and GI cases, including inflammatory bowel disease (IBD) and intestinal carcinomas. Intestinal organoids were comprehensively characterized using histology, immunohistochemistry, RNA in situ hybridization and transmission electron microscopy, and organoids mimicked the in vivo tissue environment. Physiological relevance of the enteroid system was defined using functional assays such as Optical Metabolic Imaging (OMI), the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function assay, and Exosome-Like Vesicles (EV) uptake assay, as a basis for wider applications of this technology in basic, preclinical and translational GI research.ConclusionsIn summary, our findings establish the canine GI organoid systems as a novel model to study naturally occurring intestinal diseases in dogs and humans. Furthermore, canine organoid systems will help to elucidate host-pathogen interactions contributing to GI disease pathogenesis.

Download Full-text

Method used to establish a large animal model of drug-induced acute kidney injury

Experimental Biology and Medicine ◽

10.1177/1535370220981756 ◽

2021 ◽

pp. 153537022098175

Author(s):

Si-Yang Wang ◽

Chao-Yang Zhang ◽

Guang-Yan Cai ◽

Xiang-Mei Chen

Keyword(s):

Acute Kidney Injury ◽

Animal Model ◽

Health Hazard ◽

Kidney Injury ◽

Basic Research ◽

Large Animal Model ◽

Large Animal ◽

Drug Induced ◽

Large Animal Models ◽

New Treatments

Acute kidney injury is a serious health hazard disease due to its complex etiology and lack of effective treatments, resulting in high medical costs and high mortality. At present, a large number of basic research studies on acute kidney injury have been carried out. However, acute kidney injury models established in rodents sometimes do not simulate the course of human disease well. Research in large animal models of acute kidney injury is relatively rare, and methods to build a mature model of acute kidney injury have failed. Because its kidney anatomy and morphology are very similar to those in humans, the mini pig is an ideal animal in which to model kidney disease. Nephrotoxic drug-induced acute kidney injury has a high incidence. In this study, we established models of acute kidney injury induced by two drugs (gentamicin and cisplatin). Finally, the model of cisplatin-induced acute kidney injury was developed successfully, but we found the model of gentamycin-induced acute kidney injury was not reproducible. Compared to other models, these models better represent acute kidney injury caused by antibiotics and chemotherapeutic drugs and provide a basis for the study of new treatments for acute kidney injury in a large animal model.

Download Full-text

Large animals in neurointerventional research: A systematic review on models, techniques and their application in endovascular procedures for stroke, aneurysms and vascular malformations

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19827446 ◽

2019 ◽

Vol 39 (3) ◽

pp. 375-394 ◽

Cited By ~ 17

Author(s):

Andrea M Herrmann ◽

Stephan Meckel ◽

Matthew J Gounis ◽

Leona Kringe ◽

Edith Motschall ◽

...

Keyword(s):

Systematic Review ◽

Ischemic Stroke ◽

Animal Models ◽

Translational Research ◽

Arteriovenous Malformations ◽

Vascular Malformations ◽

Large Animal ◽

Large Animal Models ◽

Large Animals ◽

Study Designs

Neuroendovascular procedures have led to breakthroughs in the treatment of ischemic stroke, intracranial aneurysms, and intracranial arteriovenous malformations. Due to these substantial successes, there is continuous development of novel and refined therapeutic approaches. Large animal models feature various conceptual advantages in translational research, which makes them appealing for the development of novel endovascular treatments. However, the availability and role of large animal models have not been systematically described so far. Based on comprehensive research in two databases, this systematic review describes current large animal models in neuroendovascular research including their primary use. It may therefore serve as a compact compendium for researchers entering the field or looking for opportunities to refine study concepts. It also describes particular applications for ischemic stroke and aneurysm therapy, as well as for the treatment of arteriovenous malformations. It focuses on most promising study designs and readout parameters, as well as on important pitfalls in endovascular translational research including ways to circumvent them.

Download Full-text

Kinetics of monocytotropic Ehrlichia infections, new insights from large animal models

10.32469/10355/15844 ◽

2011 ◽

Author(s):

Ryan Thomas Stoffel

Keyword(s):

Animal Models ◽

Large Animal ◽

Large Animal Models ◽

Kinetics Of

Download Full-text

Anti‐arrhythmic investigations in large animal models of atrial fibrillation

British Journal of Pharmacology ◽

10.1111/bph.15417 ◽

2021 ◽

Cited By ~ 1

Author(s):

Arnela Saljic ◽

Thomas Jespersen ◽

Rikke Buhl

Keyword(s):

Atrial Fibrillation ◽

Animal Models ◽

Large Animal ◽

Large Animal Models

Download Full-text

Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence

International Journal of Molecular Sciences ◽

10.3390/ijms22116092 ◽

2021 ◽

Vol 22 (11) ◽

pp. 6092

Author(s):

Bastian Amend ◽

Niklas Harland ◽

Jasmin Knoll ◽

Arnulf Stenzl ◽

Wilhelm K. Aicher

Keyword(s):

Urinary Incontinence ◽

Stress Urinary Incontinence ◽

Animal Models ◽

Clinical Situation ◽

Surgical Instruments ◽

Health Concern ◽

Large Animal ◽

Knock Out ◽

Cell Therapies ◽

Large Animal Models

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI.

Download Full-text

Animal models of hypoxic-ischemic encephalopathy: optimal choices for the best outcomes

Reviews in the Neurosciences ◽

10.1515/revneuro-2016-0022 ◽

2017 ◽

Vol 28 (1) ◽

pp. 31-43 ◽

Cited By ~ 12

Author(s):

Lan Huang ◽

Fengyan Zhao ◽

Yi Qu ◽

Li Zhang ◽

Yan Wang ◽

...

Keyword(s):

Animal Models ◽

Small Animal ◽

Underlying Disease ◽

Therapeutic Interventions ◽

Hypoxic Ischemic Encephalopathy ◽

Large Animal ◽

Large Animal Models ◽

Neurological Research ◽

Serious Disease ◽

Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE), a serious disease leading to neonatal death, is becoming a key area of pediatric neurological research. Despite remarkable advances in the understanding of HIE, the explicit pathogenesis of HIE is unclear, and well-established treatments are absent. Animal models are usually considered as the first step in the exploration of the underlying disease and in evaluating promising therapeutic interventions. Various animal models of HIE have been developed with distinct characteristics, and it is important to choose an appropriate animal model according to the experimental objectives. Generally, small animal models may be more suitable for exploring the mechanisms of HIE, whereas large animal models are better for translational studies. This review focuses on the features of commonly used HIE animal models with respect to their modeling strategies, merits, and shortcomings, and associated neuropathological changes, providing a comprehensive reference for improving existing animal models and developing new animal models.

Download Full-text

Echocardiography Evaluation of a Novel Stable Ovine Heart Failure Model Suitable for Cardiovascular Device Testing

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53824 ◽

2011 ◽

Author(s):

Peter W. Walsh ◽

Craig S. McLachlan ◽

Leigh Ladd ◽

Arie Blitz ◽

R. Mark Gillies ◽

...

Keyword(s):

Heart Failure ◽

Animal Models ◽

Large Animal ◽

Failure Model ◽

Large Animal Models ◽

Surgical Model ◽

Coronary Ligation ◽

Rapid Ventricular Pacing ◽

Heart Failure Model ◽

Underlying Pathology

Numerous large animal models of chronic cardiac ischemia have been developed to explore either pathological mechanisms and or device interventions in developed heart failure models. Traditionally chronic heart failure in large animal models such as sheep or pigs has been induced by either coronary ligation with or without reperfusion. Coronary ligation is often attempted in the open chest surgical model or more recently in the closed chest animal via angiography [1]. Both techniques can be challenging and also induce high mortality with the risk of myocardial stunning and resultant shock and or lethal arrhythmias. There is also difficulty in developing stable heart failure across cases where infarct sizes can be variable. One strategy to over come this variability has been via rapid ventricular pacing, however inducing heart failure does not induce sustained heart failure in many cases if the pacing is switched off, and additionally pacing does not induce some of the underlying pathology seen in the development of heart failure [1].

Download Full-text

Review: Tissue Engineering of Small-Diameter Vascular Grafts and Their In Vivo Evaluation in Large Animals and Humans

Cells ◽

10.3390/cells10030713 ◽

2021 ◽

Vol 10 (3) ◽

pp. 713

Author(s):

Shu Fang ◽

Ditte Gry Ellman ◽

Ditte Caroline Andersen

Keyword(s):

Animal Models ◽

Vascular Grafts ◽

Small Diameter ◽

Large Animal ◽

Large Animal Models ◽

Graft Outcome ◽

Limited Success ◽

Large Animals

To date, a wide range of materials, from synthetic to natural or a mixture of these, has been explored, modified, and examined as small-diameter tissue-engineered vascular grafts (SD-TEVGs) for tissue regeneration either in vitro or in vivo. However, very limited success has been achieved due to mechanical failure, thrombogenicity or intimal hyperplasia, and improvements of the SD-TEVG design are thus required. Here, in vivo studies investigating novel and relative long (10 times of the inner diameter) SD-TEVGs in large animal models and humans are identified and discussed, with emphasis on graft outcome based on model- and graft-related conditions. Only a few types of synthetic polymer-based SD-TEVGs have been evaluated in large-animal models and reflect limited success. However, some polymers, such as polycaprolactone (PCL), show favorable biocompatibility and potential to be further modified and improved in the form of hybrid grafts. Natural polymer- and cell-secreted extracellular matrix (ECM)-based SD-TEVGs tested in large animals still fail due to a weak strength or thrombogenicity. Similarly, native ECM-based SD-TEVGs and in-vitro-developed hybrid SD-TEVGs that contain xenogeneic molecules or matrix seem related to a harmful graft outcome. In contrast, allogeneic native ECM-based SD-TEVGs, in-vitro-developed hybrid SD-TEVGs with allogeneic banked human cells or isolated autologous stem cells, and in-body tissue architecture (IBTA)-based SD-TEVGs seem to be promising for the future, since they are suitable in dimension, mechanical strength, biocompatibility, and availability.

Download Full-text