The mucus layer is the first line of defense against infiltration of microorganisms, digestive enzymesand acids, digested food particles, microbial by-products, and food-associated toxins. This layer coats the interiorsurface of the GI tract, lubricates luminal contents and acts as a physical barrier to bacteria and other antigenicsubstances present in the lumen. The moist, nutrient-rich mucus layer adjacent to the epithelial barrier of the GItract is also essential in the maintenance of intestinal homeostasis and contains a thriving biofilm includingbeneficial and pathogenic microbial populations. However, mucus has proven difficult to study, owing to itcompositional and functional complexity and a substantial lack of either high-quality purified samples or cell-based culture systems containing mucus. This project will establish a gastrointestinal (GI) model for both harvesting physiologically relevant mucusand an epithelial culture system that possess a native mucus layer. Building on Altis' capabilities to generatemodels with greater physiological relevance using donor-derived cells, this program will establish key protocolsand workflows to ensure a reliable and reproducible mucus layer to additionally replicate in vivo GI morphologyand function. In Aim 1, we will finalize in vitro protocols for mucus production in epithelia from both the smalland large intestine (jejunum and transverse colon), which are well-described to production functionally distinctmucus. These data will establish key quality metrics enabling Altis to explore R&D studies with our industry andacademic clients in diverse aspects of early stage of drug development and the development of inflammatorydisease and microbiome research. Based on prior discussions with our pharmaceutical development customers,we view the commercial potential for this model as strong, especially given the unique capabilities of Altis' currentplatform.
Public Health Relevance Statement: Project Narrative
Mucus provides a critical component of gastrointestinal innate immunity, protecting the epithelium from
infectious and noxious agents and regulating the balance of host microbiome and inflammatory responses.
However, the lack of relevant mucus-related reagents and cell models has substantially limited GI-related drug
development and basic research. Altis Biosystems, Inc. has developed an epithelial model that can be utilized
as both a source of native GI mucus and/or an integrated cell model with a mucus layer. These models have
broad applicability to drug discovery, biomaterials development, and mechanistic studies to understand disease
pathophysiology.
Project Terms: | | | | | | | | | 