Organ-on-a-chip: the next generation tool for drug development?

Organ-on-a-chip (OoC) or Microphysiological systems (MPS) are microfluidic devices providing a controlled microenvironment for miniaturised tissues mimicking physiological architecture and function of human tissues and organs. The application of dynamic fluid flow provides gradients and mechanical cues, differentiating these systems from conventional static ones.

OoC can be generated with a range of cellular systems incorporating immortalized cell lines, primary cells or induced pluripotent stem cell (iPSC) cultures, which are placed on a chip containing a network of microchannels, allowing complete control of media. These multidimensional cellular constructs provide accurate in vitro models for the study of drug delivery, drug-cell, drug-tissue, and drug-drug interactions during pharmaceutical drug development. With significant progress made over the last two decades, OoC technology has demonstrated its potential and was selected as one for the top ten emerging technologies at the World Economic forum in 2016 (1). This also emphasises a strong need for human in vitro testing systems in the pharmaceutical industry and shows that OoC technologies have the maturity to build them.

The ambitious aim of the OoC/MPS community is to create a body-on-a-chip, by combining multiple organs to enable in vitro drug testing in a personalized medicine scenario.

But why is flow so important in a cellular tissue model?

First, similarly to what occurs in the body, the flow of media applied to the microphsiological systems enables tissue perfusion and creates shear stress. Media perfusion is the hallmark of OoC devices serving as an artificial circulatory system for the tissue on the chip and maintaining concentration gradients for nutrient transport and elimination of waste. Second, the resulting shear stress applied to the tissues gives biomechanical and mechanical cues, which are absent in static systems. As a result, the physiological cellular micro-environment is reproduced more accurately, through precise control of culture conditions enabling more cellular interactions.

Newcells, a pioneer in building and developing complex in vitro models for drug development and testing, is also incorporating flow in its models. The flagship aProximate™, proximal tubule model will shortly be available on an innovative microfluidic device. This new device is a flowplate mimicking OoC technology but at larger scale. Newcells also has the capability to build new models and generate MPS systems from a range of tissues.

(1) https://www.weforum.org/publications/top-10-emerging-technologies-of-2016/