Scientific concepts and applications of integrated discrete multiple organ co-culture technology

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.

In vitro study on aspects of molecular mechanisms underlying invasive aspergillosis caused by gliotoxin and fumagillin, alone and in combination

“…The IdMOC 96 well plates were gift from Dr. Albert P. Li, President and CEO of In Vitro ADMET Laboratories LLC, Columbia, USA. The concepts and applications of IdMOC have been reviewed 54 .…”

Shiga Toxin (Stx)-Binding Glycosphingolipids of Primary Human Renal Cortical Epithelial Cells (pHRCEpiCs) and Stx-Mediated Cytotoxicity

“…For this reason, the ex vivo production of sufficient cell quantities for the isolation of GSLs and for membrane preparations is seriously limited. However, the principal advantages over tumor-derived or immortalized cell lines lies in the more faithful mimicry of the differentiated in vivo pheno- and geno-type of primary cells providing the closest in vitro model to human organs [ 75 , 76 , 77 , 78 , 79 ]. However, primary cells exhibit stringent nutritional demands and need dedicated cell culture media, especially for cultivation under serum-free conditions requiring certain growth-promoting agents, such as growth factors, lipids, and/or hormones to compensate for serum deprivation [ 80 , 81 , 82 , 83 ].…”

Static Magnetic Fields Enhance the Chondrogenesis of Mandibular Bone Marrow Mesenchymal Stem Cells in Coculture Systems

“…In recent years, coculture techniques have been proven to be powerful tools in cartilage tissue engineering to elucidate cellular interactions so as to guide and support chondrogenesis [ 14 ]. Compared with single-cell cultures, the coculture system has shown its unique advantages with the biomimetic in vivo microenvironment [ 15 ]. The Transwell chamber facilitates the observation of cell growth and the investigation of cell-cell interactions via soluble mediators.…”