IdMOC per sostituire gli animali in farmacologia, tossicologia, nell’ADMET e nello screening di farmaci anticancro

[Loganathan Gayathri, Dharumadurai Dhanasekaran, and Mohammad A. Akbarsha. Scientific concepts and applications of integrated discrete multiple organ co-culture technology. J Pharmacol Pharmacother. 2015 Apr-Jun; 6(2): 63–70.]

Full Text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419250/

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Abstract:

“Over several decades, animals have been used as models to investigate the human-specific drug toxicity, but the outcomes are not always reliably extrapolated to the humans in vivo. Appropriate in vitro human-based experimental system that includes in vivo parameters is required for the evaluation of multiple organ interaction, multiple organ/organ-specific toxicity, and metabolism of xenobiotic compounds to avoid the use of animals for toxicity testing. One such versatile in vitro technology in which human primary cells could be used is integrated discrete multiple organ co-culture (IdMOC). IdMOC system adopts wells-within-well concept that facilitates co-culture of cells from different organs in a discrete manner, separately in the respective media in the smaller inner wells which are then interconnected by an overlay of a universal medium in the large containing well. This novel in vitro approach mimics the in vivo situation to a great extent, and employs cells from multiple organs that are physically separated but interconnected by a medium that mimics the systemic circulation and provides for multiple organ interaction. Applications of IdMOC include assessment of multiple organ toxicity, drug distribution, organ-specific toxicity, screening of anticancer drugs, metabolic cytotoxicity, etc.

Conclusioni:

“The IdMOC technology is a simple and new-generation in vitro experimental system which does not require any sophisticated laboratory equipment for the evaluation of distribution, metabolism, and toxicity of a xenobiotic. Co-culture of multiple cell types of the same organ or multiple organs in a physically discrete manner allows the system to interact and helps to predict the multiple endpoints. Use of primary human cells and incorporation of metabolic cytotoxicity to the in vitro system provides an insight to the scientific community that IdMOC is a physiologically relevant model for risk assessment. The embodiment of wells-within-well concept in IdMOC technology has promoted in vitro technique from routine two-dimensional cell culture to mimic, to a great extent, the real in vivoconditions. Thus, IdMOC is an innovative and less time-consuming model that could replace animal testing methods perhaps to comply with the changing regulatory needs. In vitro approach has always been an adoptable technique and readily procures many in vivo key features. Thus, the technique could overcome the uncertainty of animal testing and withstand for a long period to reduce and replace the use of animals in scientific research. However, novel inventions and new methodologies will never stop until the in vitro condition matches or supersedes the in vivo condition. The future of cell culture could be the virtual human-on-chip which may simulate a complete human, but in a simple magnitude. IdMOC has a great potential simulating humans in vivo using in vitro conditions and this technique can be adopted by all researchers who are efficiently carrying out conventional in vitro cell culture in the laboratory.”

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