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

Gayathri L, Dhanasekaran D, Akbarsha MA - J Pharmacol Pharmacother (2015 Apr-Jun)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Bharathidasan University, Tiruchirappalli 620024, Tamil Nadu, India ; Mahatma Gandhi Doerenkamp-Center, Bharathidasan University, Tiruchirappalli - 620024, Tamil Nadu, India.

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.

No MeSH data available.


Related in: MedlinePlus

(a) The human body is conceptualized here as multiple organs connected by blood, the principle adopted in the IdMOC system. (b) A cross-section of the IdMOC plate is depicted, demonstrating the culture of multiple cell types (cells A–C) in physically separated cultures in different wells but later interconnected by flooding of a common medium. The IdMOC, thus, mimics the humans in vivo, with multiple organs as physically separated entities connected by a common fluid (blood in vivo; the overlay medium in the IdMOC)[18]
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Figure 1: (a) The human body is conceptualized here as multiple organs connected by blood, the principle adopted in the IdMOC system. (b) A cross-section of the IdMOC plate is depicted, demonstrating the culture of multiple cell types (cells A–C) in physically separated cultures in different wells but later interconnected by flooding of a common medium. The IdMOC, thus, mimics the humans in vivo, with multiple organs as physically separated entities connected by a common fluid (blood in vivo; the overlay medium in the IdMOC)[18]

Mentions: The main advantage of the system is design of the culture plate. IdMOC uses wells within well concept which means the plate has chambers/large containing wells, with each having six small inner wells. This kind of plate design allows culture of different cell types from different organs or different cell types from the same organ separately in the small inner wells. In the six inner wells of each chamber, one can culture six different cell types, one in each well, three different cell types each in duplicate or two different cell types each in triplicate. After culturing the two or more cell types in the six small inner wells, in their respective media, they can be interconnected by filling the chamber/large containing well with a universal medium which contains the drug/xenobiotic compound at a certain concentration for a defined incubation period. Then the xenobiotic-treated cells can be subjected to assays and the medium can be used to analyze the metabolite(s) of the parent xenobiotic compound.[9] Figure 1 represents the concept of IdMOC and the schematic design of the IdMOC plate.[10]


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

Gayathri L, Dhanasekaran D, Akbarsha MA - J Pharmacol Pharmacother (2015 Apr-Jun)

(a) The human body is conceptualized here as multiple organs connected by blood, the principle adopted in the IdMOC system. (b) A cross-section of the IdMOC plate is depicted, demonstrating the culture of multiple cell types (cells A–C) in physically separated cultures in different wells but later interconnected by flooding of a common medium. The IdMOC, thus, mimics the humans in vivo, with multiple organs as physically separated entities connected by a common fluid (blood in vivo; the overlay medium in the IdMOC)[18]
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4419250&req=5

Figure 1: (a) The human body is conceptualized here as multiple organs connected by blood, the principle adopted in the IdMOC system. (b) A cross-section of the IdMOC plate is depicted, demonstrating the culture of multiple cell types (cells A–C) in physically separated cultures in different wells but later interconnected by flooding of a common medium. The IdMOC, thus, mimics the humans in vivo, with multiple organs as physically separated entities connected by a common fluid (blood in vivo; the overlay medium in the IdMOC)[18]
Mentions: The main advantage of the system is design of the culture plate. IdMOC uses wells within well concept which means the plate has chambers/large containing wells, with each having six small inner wells. This kind of plate design allows culture of different cell types from different organs or different cell types from the same organ separately in the small inner wells. In the six inner wells of each chamber, one can culture six different cell types, one in each well, three different cell types each in duplicate or two different cell types each in triplicate. After culturing the two or more cell types in the six small inner wells, in their respective media, they can be interconnected by filling the chamber/large containing well with a universal medium which contains the drug/xenobiotic compound at a certain concentration for a defined incubation period. Then the xenobiotic-treated cells can be subjected to assays and the medium can be used to analyze the metabolite(s) of the parent xenobiotic compound.[9] Figure 1 represents the concept of IdMOC and the schematic design of the IdMOC plate.[10]

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Bharathidasan University, Tiruchirappalli 620024, Tamil Nadu, India ; Mahatma Gandhi Doerenkamp-Center, Bharathidasan University, Tiruchirappalli - 620024, Tamil Nadu, India.

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.

No MeSH data available.


Related in: MedlinePlus