A main breakthrough can be made by combining the power of stem cells, genetics microtechologies, microfluidics, biomaterials, and 3D printing, to provide cells with spatio-temporal guidance patterns, structured down to the single cell scale, and thus help to reconstruct functional micro-organs with a much stronger predictive power than current in vitro models, and much less risk for translation to humans, than animal experimentation.
- The big picture: Genome research and cell biology have made tremendous progress, which help to better understand diseases, and yield new families of drugs and therapeutic strategies. In order to be transformed into drugs, however, these progresses still have to go through a lengthy and extremely costly validation route, passing by animal trials, which raise ethical problems and involve problematic transposition to humans, and human clinical trials, which still involve some risks in spite of extreme caution and very strict regulations. The development of stem cells and human induced pluripotent cells (iPSC) raise the hope to reduce these risks and accelerate translation from research to clinics, but there is still a very large gap between tests on cell cultures and what happens in an individual.
iPSC also raised the dream to allow a transition from transplants to organ replacement, an explicit target of the strategic foresight EC document for 2018-2020
but there is still a gulf between the current assembly of cells that can be cultured, and a functional organ that could be implanted in a human.
- The work needed: In order to overcome the gap described above, attempts have been mode to develop “organoids”, i.e. multicellular assemblies, using the self-assembly properties of cells to reconstitute in vitro micro-organs in which the effect of diseases and of drugs could be observed in a situation closer to the full organism, and without the biases inherent to the differences between animals and humans. These models, however, are still of limited realism, because they lack the elaborate spatio-temporal guidance that lead cells into the structure of normal tissues and organs. A main breakthrough can be made in this area, however, by combining to the power of stem cells and genetics already mentioned above, that of microtechologies, microfluidics, biomaterials, and 3D printing: thanks to these technologies, it will be indeed possible to provide cells with spatio-temporal guidance patterns, structured down to the single cell scale, and thus help to reconstruct functional micro-organs with a much stronger predictive power than current in vitro models, and much less risk for translation to humans, than animal experimentation. Biotech SMEs will be needed to translate these results towards bigger players such as the pharma industry.
- The opportunity: This development is timely, because both stem cells research and microfluidics emerge from infancy, and can now be harnessed to major tasks relevant to human health. The development of cell biology in microfluidic systems is indeed exploding, but so far model organs remained limited to rather simple systems, only a handful of which use human iPSC. This development is also urgent, because the pharmaceutical industry has recognized the need to leave 2D cells culture for 3D systems, but remains today limited to non-organized or poorly organized spheroids, still very far from the behavior of cells in real organs. To address this challenge, the NIH, in collaboration with DARPA and FDA, has launched a multi-millions coordinated initiative to develop “Tissue-chips” representative of various organs of the human body (see e.g. (https://www.youtube.com/watch?v=zVlEr8c-OJk&feature=youtu.be).
It is thus key to the competitivity of the European Industry, and the independence of the European health system, to also be at the forefront of this new frontier, using the specific strengths of Europe in microfluidics, stem cells and fundamental biology, and notably innovative materials not well considered in the American initiative. Besides its key importance for pharmaceutical research, the development of tissue and organs on chip involving biocompatible materials will also be mandatory to allow a transition from transplants to organ replacement, a target identified in the EC strategic foresight document “ Towards the third strategic programme of Horizon 2020”