REPROCELL is able to access almost all regions of the GI tract including stomach and the small and large intestine. Tissue is available from both healthy and diseased individuals and tissues are available from patients suffering from inflammatory bowel disease (IBD).
Our gastrointestinal assays allow REPROCELL to investigate the effects of drugs on the human gastrointestinal system in a number of ways, including:
REPROCELL is able to assess potential human GI adverse effects using fresh human tissues and can make comparisons to effects in preclinical species in order to understand the translation from animals to humans
Effects on permeability can be assessed using our Ussing Chamber methodology. It is also possible to determine the effects of your test compound on the enteric nervous system or ‘mini-brain’, as this is where much of the regulation of the GI tract occurs. Our organ bath model can be used to determine adverse effects on gut motility. Inflammation of the gut is also a regular unwanted side effect of many drug compounds, which can be detected using our mucosal organoculture model.
Maintenance of drug therapies is driven to a large extent by the existence of adverse effects that deter patients from complying with regimens. For example, a major issue with treatments for Alzheimer's disease is the gastrointestinal effect of anti-acetylcholinesterases such as Galantamine, which increase cholinergic activity in the brain but may also do so in the GI tract (see graph below).
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Biopta can access tissues from patients suffering from inflammatory bowel disease (IBD) like Crohn’s disease or Ulcerative Colitis. Inflammation of mucosa is a defining feature of these conditions. Biopta can secure tissue from these patients and using our organoculture model we are able to examine production of cytokines or other endogenous mediators at baseline level and in response to your test compounds.
Gastrointestinal biopsies (5mm2) are prepared and set up in media as per the image above. The biopsies can be maintained for 24h (see image below) and supernatant samples can be taken at various time points for the measurement of cytokine and chemokine levels in the presence or absence of test compound.
Colon explant histopathology maintained over a 24 hour period. At 0 hour good crypt morphology with intact lamina propria and muscularis mucosa can be sees. After 24 hours crypt morphology and muscularis mucosa were maintained. Slight degradation of epithelial structure but generally intact.
The GI tract is a huge target for pharmaceutical development, and REPROCELL is able to provide efficacy information on treatments designed to affect changes in motility, inflammation or drug absorption.
Inflammation of the mucosa is a defining feature of many GI disorders, most notably Crohn’s disease and ulcerative colitis. REPROCELL can source tissue from these patients and using our ex vivo culture model we are able to examine production of cytokines or other endogenous mediators at baseline level and in response to your test compounds.
Prediction of gut permeability is also possible using human small intestinal tissue. Rather than use the Caco-2 cell line which can be inaccurate when used to predict the absorption of test compounds that are actively or poorly absorbed by the gut, REPROCELL uses the small intestinal mucosa to determine permeability or bioavailability using the Ussing chamber.
GI contractility studies are useful in determining how compounds affect GI motility in either a therapeutic capacity (evaluation of drugs for motility disorders) or from a safety perspective. Although there has been much progress in the diagnosis and therapy of these diseases, curative treatment options are still limited and long-term outcome often remains unsatisfactory.
The contractile properties of GI smooth muscle can be assessed using in vitro preparations of nearly all the GI tract regions including esophagus, lower esophageal sphincter, stomach, small intestine or colon. Full thickness GI muscle strips can be dissected to obtain either circular or longitudinal muscle strips and both direct responses (agonist and antagonist effects on contraction and relaxation) and modification of nerve-evoked responses using electrical field stimulation, can be evaluated.
Figure 1. Carbachol causes a concentration-dependent constriction of human colonic muscle strips.
Figure 2. Carbachol enhances the magnitude of the EFS induced contractions of human colonic muscle strips orientated in both the circular and longitudinal plains.
Predictive Drug Discovery Assays