Intestinal epithelium is the fastest dividing tissue in the body, and the health of the cells can be easily impacted by environmental toxins and drugs. This organ system is therefore a prime target for biological testing of medicinal compounds, prebiotics and microbial products. An in vitro gut model that can precisely predict these impacts will reduce the burden of testing by diminishing reliance on animal models, minimizing the number of overlapping assessments and helping to eliminate unnecessary testing. To meet this need, Altis Biosystems Inc., an early stage biotechnology company, will collaborate with scientists at University of Washington to develop a novel 2-dimensional (2D) crypt platform that emulates the gut epithelium. Human primary intestinal epithelial stem cells will be patterned on the platform to mimic a gut epithelium possessing a stem-cell niche, and migratory proliferating and differentiating cells. This planar 2D platform will enable high-content/high-throughput assays in a rugged and reproducible manner. In this Phase I SBIR, this collaboration will generate 2D crypts with intervening regions of a differentiated cell monolayer, optimize the platform with a focus on quantitative strategies to benchmark performance, and perform small scale screens to demonstrate feasibility to advance to a Phase 2 project. The goal is to develop and benchmark a quantitative in vitro method that will enable investigators to efficiently evaluate the impact of compounds on intestinal stem cell proliferation and differentiation.
Public Health Relevance Statement: Project Narrative The novel two-dimensional crypt gastrointestinal organ-on-chip platform will have broad applications in enhancing the predictability of pre-clinical testing and reduce reliance on animal and clinical studies.
Project Terms: Age; ages; Animals; Biological Assay; Assay; Bioassay; Biologic Assays; Biomedical Engineering; bio-engineered; bio-engineers; bioengineering; Biotechnology; Biotech; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Cell Culture Techniques; cell culture; Cell Differentiation process; Cell Differentiation; Cells; Cell Body; Child; 0-11 years old; Child Youth; Children (0-21); youngster; Clinical Research; Clinical Study; Clinical Trials; Diabetes Mellitus; diabetes; Pharmaceutical Preparations; Drugs; Medication; Pharmaceutic Preparations; drug/agent; Ethics; ethical; Goals; Health; Heart; Human; Modern Man; In Vitro; Inflammation; Intestines; Intestinal; bowel; Liver; hepatic body system; hepatic organ system; Lung; Lung Respiratory System; pulmonary; Metabolism; Intermediary Metabolism; Metabolic Processes; Methods; Mission; Modernization; United States National Institutes of Health; NIH; National Institutes of Health; Physiology; Play; Publishing; Radiologic Health; Radiological Health; Research Personnel; Investigators; Researchers; Risk; Role; social role; stem cells; Progenitor Cells; Technology; Testing; Tissues; Body Tissues; Toxic Environmental Substances; Environmental Toxin; Toxic Environmental Agents; environmental toxicant; Toxicology; Universities; Genetic Variation; Genetic Diversity; Washington; Woman; Work; Gender; base; Organ; improved; Phase; Biological; Medical; Evaluation; intestinal epithelium; insight; Individual; Collaborations; Image Cytometry; Nature; cognitive function; Scientist; human tissue; Oral; cell type; Pattern; System; Organ System; body system; Goblet Cells; gastrointestinal; Enteroendocrine Cell; Best Practice Analysis; Benchmarking; interest; Performance; Animal Models and Related Studies; model of animal; model organism; Animal Model; microbial; Toxicities; Toxic effect; Speed; Human Biology; novel; Enterocytes; Devices; Gut Epithelium; gastrointestinal epithelium; Modeling; drug development; High Throughput Assay; high throughput screening; monolayer; hormonal regulation; hormone regulation; adult stem cell; Pharmaceutical Agent; Pharmaceuticals; Pharmacological Substance; Pharmacologic Substance; Animal Testing; Biological Testing; pre-clinical testing; Preclinical Testing; Proliferating; Reproducibility; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Tissue Model; Characteristics; Development; developmental; safety study; stem cell differentiation; microbiome; stem cell niche; cost; intestinal crypt; Minority; prebiotics; Outcome; Population; Microbe; two-dimensional; 2-dimensional; human disease; novel therapeutics; new drug treatments; new drugs; new therapeutics; new therapy; next generation therapeutics; novel drug treatments; novel drugs; novel therapy; stem; commercialization; patient population; in vitro testing; biobank; biorepository; screening; precision medicine; precision-based medicine; gut microbiome; GI microbiome; digestive tract microbiome; enteric microbiome; gastrointestinal microbiome; gut-associated microbiome; intestinal biome; intestinal microbiome; efficacy study; predictive test; predictive assay; organ on a chip; organ on chip; microphysiology system; microphysiologic model; microphysiologic platform; microphysiologic system; microphysiology model; microphysiology platform; epithelial stem cell; epithelial progenitor cell; stem cell proliferation; progenitor cell proliferation
