Organs on Chips: human disease models
24-28 September, 2012
“Organs on Chips” are multicellular mini-organs grown in a microfluidic chips that in vitro reproduce complex, integrated organ-level physiological and pathological processes. Organs on Chips could, in the future, be used as human disease models for the discovery and development of drugs as well as toxicity testing. A such, they could be used instead of / in addition to currently used models based on primary tissues and cells in culture dishes or animal models, that often are not representative of human disease and pathophysiology. The main objective of this workshop was to develop a common view on the required combinations of methods and technologies for creating “Organs-on-Chips” for different organs and diseases.
Results of the workshop
A number of different technological platforms that could be suitable for Organ on a Chip application were presented during the workshop: platforms based on compartmentalized microfluidic devices, high-throughput microdroplet technologies, hydrogel structuring technologies, and platforms allowing for controlling mechanical environment of cells and tissues. These platforms have already been applied to mimic, on a basic level, the function of various organs: lungs, heart, skin, bloodvessels, gut, breast, spleen. The potential to combine (a number of) those platforms was discussed.
The source of the cells for Organs on Chips is important, and depending on the application and use can be primary cells, tissue slices, hES (human Embryonic Stemcells), iPS (induced Pluripotent Stemcells). The latter cell type provide the very interesting possibilities of creating, in a reproducible manner, disease models with specific genetic backgrounds. Standardization of iPS cell lines and culture conditions and differentiation protocols will be necessary and has started.
Another important topic of the workshop was about readouts: what to measure and analyze? All kinds of microscopy technologies are expected to be highly valuable for (high throughput) readout tests. Reporter systems enable real time measurements of for example oxygen and lactate, but also specific gene transcription. Still lacking is high resolution 3D fluorescent imaging, required to real time measure fluorescent signal at a single (sub)cell level.
The pharmaceutical industry and agencies such as The NIH, DARPA and the FDA are highly interested in this developing field, and especially stimulate development of a multi-organ-on-a-chip, as well as driving development of high throughput model systems with high throughput read-out technologies.
As a follow-up to the Workshop, a special issue on “Organs on Chips” will be published by the Royal Society of Chemistry in “Lab on a Chip” and “Integrative Biology”, which will include a meeting report of the Lorentz Workshop.
Format and structure of the program
The very friendly and inviting atmosphere of the Lorentz Center, the cozy common room, including free drinks, each participant his or her own “Lorentz mug” to drink from, the barbecue on the beach, and the mixture of lectures and discussion time created a very stimulating and pleasant setting, where participants really felt at home, and were willing to very openly share their results, including those they had doubts about. The poster presentations and the poster prize contest were very successful to involve young scientists and give them a stage. Despite the absence of any formal confidentiality agreement, this appeared to be the case for both academic and commercial participants, and resulted in unique discussions, friendships and multiple future scientific collaborations.
The mixture of participants with a wide range of backgrounds ranging from physicists, chemists, engineers, biologists, medical specialists (oncologists, pathologists), representatives from pharmaceutical research, in-vitro-diagnostics (IVD) companies, and a representative from the US regulatory authorities, enabled unique interactions and exchange of experience and expertise, and definitely contributed to the success of the workshop.
Hans Clevers (Utrecht, Netherlands)
Don Ingber (Cambridge, USA)
Christine Mummery (Leiden, Netherlands)
Anja van de Stolpe (Eindhoven, Netherlands)
Jaap den Toonder (Eindhoven, Netherlands)