standardization-maintenance-3d-canine-hepatic-intestinal-organoid

Standardization and Maintenance of 3D Canine Hepatic and Intestinal Organoid Cultures for Use in Biomedical Research

Dogs develop complex multifactorial diseases analogous to humans, including inflammatory diseases, metabolic diseases, and cancer. Therefore, they ...

canine-intestinal-organoids-in-a-dual-chamber-permeable-support-system

Canine Intestinal Organoids in a Dual-Chamber Permeable Support System

The permeable support system is typically used in conjunction with traditional two-dimensional (2D) cell lines as an in vitro tool for evaluating the oral ...

Iowa State University

The advent of the genome editing era brings forth the promise of adoptive cell transfer using engineered chimeric antigen receptor (CAR) T cells for targeted cancer therapy. CAR T cell immunotherapy is probably one of the most encouraging developments for the treatment of hematological malignancies. In 2017, two CAR T cell therapies were approved by the US Food and Drug Administration: one for the treatment of pediatric acute lymphoblastic leukemia (ALL) and the other for adult patients with advanced lymphomas. However, despite significant progress in the area, CAR T cell therapy is still in its early days and faces significant challenges, including the complexity and costs associated with the technology. B cell lymphoma is the most common hematopoietic cancer in dogs, with an incidence approaching 0.1% and a total of 20-100 cases per 100,000 individuals. It is a widely accepted naturally occurring model for human non-Hodgkin's lymphoma. Current treatment is with combination chemotherapy protocols, which prolong life for less than a year in canines and are associated with severe dose-limiting side effects, such as gastrointestinal and bone marrow toxicity. To date, one canine study generated CAR T cells by transfection of mRNA for CAR domain expression. While this was shown to provide a transient anti-tumor activity, results were modest, indicating that stable, genomic integration of CAR modules is required in order to achieve lasting therapeutic benefit. This commentary summarizes the current state of knowledge on CAR T cell immunotherapy in human medicine and its potential applications in animal health, while discussing the potential of the canine model as a translational system for immuno-oncology research.

CAR T Cell Immunotherapy in Human and Veterinary Oncology: Changing the Odds Against Hematological Malignancies.

Large animal models, such as the dog, are increasingly being used for studying diseases including gastrointestinal (GI) disorders. Dogs share similar environmental, genomic, anatomical, and intestinal physiologic features with humans. To bridge the gap between commonly used animal models, such as rodents, 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.

Derivation of adult canine intestinal organoids for translational research in gastroenterology.

Pet foods may be formulated with decreased starch to meet consumer demands for less processed diets. Fats and oils may be added to low-starch diets to meet energy requirements, but little is known about its effects on canine health. The study objective was to evaluate the effects of feeding healthy adult dogs low carbohydrate, high-fat diets on apparent total tract digestibility, fecal characteristics, and overall health status. Eight adult Beagles were enrolled in a replicated 4 × 4 Latin Square design feeding trial. Dogs were randomly assigned to one of four dietary fat level treatments (T) within each period: 32% (T1), 37% (T2), 42% (T3), and 47% (T4) fat on a dry matter basis. Fat levels were adjusted with the inclusion of canola oil added to a commercial diet. Each dog was fed to exceed its energy requirement based on NRC (2006). Blood samples were analyzed for complete blood counts, chemistry profiles, and canine pancreatic lipase immunoreactivity levels. Apparent total tract digestibility improved (P < 0.05) as the fat level increased for dry matter, organic matter, fat, and gross energy. Fecal output decreased as levels of fat increased in the diet (P = 0.002). There was no effect of fat level on stool quality or short-chain fatty acid and ammonia concentrations in fecal samples (P ≥ 0.20). Blood urea nitrogen levels decreased with increased fat level (P = 0.035). No significant differences were seen in canine pancreatic lipase immunoreactivity (P = 0.110). All blood parameters remained within normal reference intervals. In summary, increased dietary fat improved apparent total tract digestibility, did not alter fecal characteristics, and maintained the health status of all dogs.

Apparent total tract digestibility, fecal characteristics, and blood parameters of healthy adult dogs fed high-fat diets.

Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years. Because of its high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. The development of innovative molecular and cellular tools is necessary to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.

Agnes Bourgois-Mochel

Department of Veterinary Clinical Sciences,
College of Veterinary Medicine,
Department of Veterinary Clinical Sciences, College of Veterinary Medicine

Iowa State University

Standardization and Maintenance of 3D Canine Hepatic and Intestinal Organoid Cultures for Use in Biomedical Research

Canine Intestinal Organoids in a Dual-Chamber Permeable Support System

Agnes Bourgois-Mochel

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Veterinary Clinical Sciences,College of Veterinary Medicine,Department of Veterinary Clinical Sciences, College of Veterinary Medicine

Iowa State University

Standardization and Maintenance of 3D Canine Hepatic and Intestinal Organoid Cultures for Use in Biomedical Research

Canine Intestinal Organoids in a Dual-Chamber Permeable Support System

Department of Veterinary Clinical Sciences,
College of Veterinary Medicine,
Department of Veterinary Clinical Sciences, College of Veterinary Medicine