Platform Technologies – Overview
Predictive Drug Discovery Services
REPROCELL offers a wide range of experimental techniques in isolated fresh tissues, including the ability to conduct comparative pharmacology studies to examine translation from preclinical species to humans.
The illustration below summarises our main techniques and the associated endpoints.
Each of these areas provides valuable information on a range of endpoints:
- Tissue baths – an essential method for pharmacologists that allows investigations of smooth muscle, cardiac muscle or skeletal muscle and nerve/muscle interactions. Isolated tissues are suspended within a fluid-filled, heated and gassed environmental chamber and measurements of force generation are recorded via sensitive force transducers. Typical endpoints measured included vasoconstriction, bronchodilatation, gastrointestinal motility or bladder activity. Suitable for a wide range of tissue types and sizes, from strips of muscle down to small airways or blood vessels of approximately 2 mm diameter. The technique continues to be a mainstay of in vitro pharmacology and has been part of many key discoveries; the Nobel prize winner Professor Robert Furchgott conducted experiments demonstrating endothelium-derived relaxing factor using such equipment.
- Wire myographs – a miniaturised version of tissue baths, which allows investigations in tissues smaller than can be mounted in tissue baths. The small vessel myograph was originally developed by Professor Mike Mulvaney as a method to sensitively measure vasoactivity of resistance arteries; the technique can however also be used to investigate small airways (bronchi). The tissues are mounted horizontally within a environmental chamber and ultra-sensitive force transducers provide information on the contractile state of the tissues.
- Ussing chambers – allow investigations in intact mucosal tissues including the electrical, metabolic and absorptive properties of the membrane. Endpoints measured include in vitro permeability of drug compounds (Papp), phase I and II metabolism (e.g. CYP3A4 mediated metabolism of drugs), short-circuit current (Isc), potential difference (PD) measurements and transepithelial resistance (TEER).
- Perfusion myographs – Biopta's patented PM-1 instrument allows investigations of isolated perfused tubular tissues such as blood vessels and ureters. By sensitively regulating pressure and flow within the tissue and delivering drugs intraluminally or extraluminally, the PM-1 offers a physiological relevant environment for measurements of tissue constriction or dilatation or changes in permeability.
- Ex vivo cultures (organocultures) – Biopta offers a range of intact fresh tissue culture systems that can be customised to suit your requirements. Such assays are phenotypically accurate when using fresh healthy or diseased human tissues. Biopta ethically sources tissues from patients with psoriasis, inflammatory bowel disease and COPD, which are placed in culture for hours to days, allowing measurement in a range of functional endpoints such as cytokine/chemokine production, gene expression or immunohistochemistry.
Whatever tissue or species you are working on, REPROCELL can help translate your findings to humans. View our catalogue of assays in human isolated functional tissues, or contact our scientists today to discuss a customised approach that will demonstrate the efficacy, safety and ADME properties of your compounds.