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'Organ-on-a-chip' device to mimic liver function
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The liver is a major cause of late-stage failure of new drugs due to toxicity reactions in humans that are not detected in animals. There is currently a lack of adequate in vitro liver tissue models that could be used to help overcome this limitation. However, a new study from researchers from the Center for Engineering in Medicine at the Massachusetts General Hospital has taken a step forward. The researchers used a novel ultrathin collagen matrix assembly which maintained liver cells in a fully functional and differentiated form. The study is published in the current issue of the journal Technology.

This microscale ‘organ-on-a-chip’ device is a prime example of 3-D microtissue biotechnological engineering. The use of collagen, a biologically relevant extracellular matrix molecule, allows liver cells to be provided with the correct extracellular matrix cues to maintain their morphology and This provides an in vitro tool for re-creating liver micro-tissues by layering together all the different liver cell types. This would facilitate study of healthy liver physiology and liver diseases. Importantly, new and experimental drug liver toxicity could be dissected before moving to animals or the clinic.

Senior author Dr Martin Yarmush explains: "This is a clever combination of the well-known layer-by-layer deposition technique for creating thin matrix assemblies and collagen functionalization chemistries that will really enable complex liver microtissue engineering by replicating the physiological cues that maintain the state of liver cell differentiation….The ultrathin collagen matrix biomaterial and its ability to keep liver cells functional for longer periods of time in chip devices will undoubtedly be a useful tool for creating liver microtissues that mimic the true physiology of the liver, including cell and matrix spatial geometries".

Sources:

McCarty, W.J., Usta, O.B., Luitje, M., Sundhar Bale, S., Bhushan, A., Hegde, M., Golberg, I., Jindal, R. and Yarmush, M.L. (2014). A novel ultrathin collagen nanolayer assembly for 3-D microtissue engineering: Layer-by-layer collagen deposition for long-term stable microfluidic hepatocyte culture. Technology 02, 67 (2014). DOI: 10.1142/S2339547814500083.

Press release: World Scientific; available at http://www.worldscientific.com/page/pres...4-04-02-07 [Accessed 4 April 2014].

Accompanying figure: “An ultrathin collagen matrix assembly maintained the morphology and function of primary liver hepatocytes in a microfluidic organ-on-a-chip device for two weeks. Three images of the hepatocytes after two weeks in a microfluidic device: A phase contrast image of cell morphology at two weeks showing dense cytoplasm, distinct nuclei, and bright cell borders; bile canalicular network development (red); and cell nuclei (blue) and actin (green) organization demonstrating cell polarity.” Credit: William McCarty, the Center for Engineering in Medicine at the Massachusetts General Hospital, Harvard Medical School, and the Shriners Hospitals for Children-Boston).

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