Human Intestinal Cell Subtypes can be Key to Effective Preclinical Studies

New models of translational biological systems are indispensable to the advancement of biomedical research. In comparison to animal models or immortalized cell models, human primary cells demonstrate increased physiological relevance in terms of response, efficacy, and toxicity (Zachos, 2016). In particular, reliable and accurate in vitro and ex vivo models of intestinal function are highly sought after to evaluate for potency and
toxicity of new drug candidates during discovery (Liu, 2016; Wallach, 2017).

The intestine is a digestive organ that is composed of two segments, the small intestine and the large intestine. Each of these segments is further subdivided, with the small intestine consisting of the duodenum, jejunum, and ileum, and the large intestine consisting of the cecum, ascending, transverse, descending and sigmoid colon, rectum, and anal canal. Each of the intestinal regions is known to perform a specific function, and descriptions of each are beyond the scope of this post, but there are plenty of freely available online  resources that can be consulted to learn more (see here for instance).    

Primary cells derived from the small and large intestines of healthy humans have been shown to highly recapitulate intestinal function and structure, and therefore, the use of primary human intestinal cell models during the drug discovery and development  phases can help mitigate translational risk before initiating clinical studies.

Intestinal cell models can be used for several purposes, including the study of permeability and transport of orally administered drugs and to evaluate for efficacy or toxicity earlier in preclinical development. Furthermore, given the prevalence of human intestinal disease and a high unmet medical need for many of them, the need for better clinically relevant models of the intestinal system are needed (Hynds, 2013). Importantly, primary intestinal cells offer researchers the option to employ subtypes of cells that have been isolated from different portions of the intestine, and therefore are powerful tools for preclinical studies including in the search for potential therapeutic targets that are relevant to the pathogenesis across  the spectrum of intestinal diseases, such as celiac disease, Crohn’s disease, inflammatory bowel syndrome, and even infections (e.g., Salmonella or E. coli) (Mifflin, 2011; Mochel, 2018; Piscaglia, 2014).

Intestinal epithelial and myofibroblast cells are two intestinal cell types that can be used to advance preclinical studies. The epithelium plays a critical role in the absorption, digestion, and retention of nutrients, as well as provide immune defense against toxins within the intestine (Santaolalla, 2011). This single layer of cells forms an interface between the external and internal host environments- absorbing beneficial substances while restricting the entry of harmful substances. Subepithelial myofibroblasts provide further resistance to intestinal immune threats and help in regeneration of the intestinal epithelial. Intestinal myofibroblasts contribute to tissue growth and repair, would healing, angiogenesis, immune response, inflammation, tumorigenesis, fibrosis, and more (Mifflin, 2011).

These primary cell subtypes have been shown to effectively model intestinal epithelium physiology and gastrointestinal disease processes (Hynds, 2013; Zachos, 2016), enabling both the study of host organism-pathogen interactions and the search for therapeutic targets. Additionally, both intestinal epithelial cells and myofibroblasts are valuable assets in preclinical drug candidate screening and can be used to model or measure orally administered drug response. In particular, intestinal myofibroblasts are useful in toxicological studies, absorption studies, and gene expression studies.

Prior to initiating a study with primary human intestinal cells, researchers should conduct due diligence to identify a supplier that is reliable, has an established organ procurement network, and is experienced in providing high-quality primary human cells. Novabiosis is a leading provider of several cryopreserved human cells from multiple organ types for research applications, drug discovery, and drug development. They offer a wide selection of primary human intestinal cells isolated from specific intestinal regions within normal, healthy and diseased donors. These include intestinal epithelial cells (duodenum, ascending colon, descending colon, transverse colon) and myofibroblast (ascending colon, descending colon, duodenum, ileum, jejunum, transverse colon). Primary human intestinal cells are ideal to study intestinal physiology, model the pathophysiology of gastrointestinal disease, and evaluate the efficacy or toxicity of orally administered drugs during preclinical development.