Tools for Tissue Quantification by Imaging: High Content Histopathology of human and artificial tissues – TooTiQuantI

Quantitative cell biology based on image analysis underwent a very important development in the recent years, allowing the birth of tools adapted to an industrial use in the field of drug discovery. This industrialization of “cell biology by imaging” is coined “High Content Analysis” (HCA) or “High Content Screening” (HCS) by opposition to the lower content of predictive information yielded by methods that rely on simplified test systems instead of intact cells. Application of HCA has however rapidly met the limitation of its biological model: cell lines grown on plastic surfaces lack the key properties deriving from the cellular interplay that take place in an organized tissue, urging for the development and the use of tissues as models amenable to HCA. Interestingly, while systematic genetic and genomic approaches were conducted at the clinical level to identify genetic modifications or expression signatures within tissues associated with pathology their conversion into cellular biomarkers and their genuine quantitative exploration at the organized tissue level is still very dificult on an industrial basis due to a missing technology . Bridging this gap deals with being able to apply HCA to tissue analysis as a systematic industrial tool.
The core objective of the present project is thus to make HCA applicable to both Human and artificial tissues in order to extract genuine and complex cytometric data that cannot be detected by the human eye and that can give access to previously ignored key predictive contents. This is a particularly challenging goal since it involves the combined development/adaptation and global optimization of all the steps involved (tissue sampling/synthesis, sample “parallel organization” strategy, marking methodology, automated imaging and analysis) and thus requires an organized multidisciplinary team with Pathologists, Molecular Oncologists, Physicists, Computer Scientists and Cell Biologists.
The interdisciplinarity of the team we have assembled also warrants that the proposed methodological development is completely connected to and guided by very topical biomedical research objectives from cancer research and liver cell toxicology.
Thus, aside from final products (see below), the project will also generate original scientific data will be patented and/or published in international scientific journals.
The main final products of the project will be: (i) a new improved cancer biomarker tissue analysis service offer that will be made available to the pharma industry, (ii) a new predictive liver toxicology service offer based on artificial liver microtissue production and analysis that will also be made available to the pharma industry, (iii) a new methodology prototype “suite”, eventually packageable as a kit with standard operation procedure and device, for producing and bringing large series of microtissues to quantitative imaging (target: industry and academic labs), (iv) a new tissue quantification platform prototype based on photothermal imaging (target: Clinical Pathology labs).