In 2007, Japanese Nobel Prize winner Shinya Yamanaka was the first to create 'pluripotent' stem cells from adult human cells. As a result, human embryos were no longer needed to form stem cells. And pluripotency means that every stem cell can give rise to all the different cells in the human body, outside the body itself. In theory, this means that it becomes possible to grow all body tissues outside the body and examine them on a chip for diseases and the effect of medicinal therapy. To achieve such breakthroughs, research is needed in which fundamental science is linked to very high technology, such as nanotechnology. The Netherlands appears to be an international leader in this domain. Therefore, and because the role of technology is so prominent here, there is an interest for FHI companies to follow these developments and possibly be involved in the research in which significant amounts are invested by the Dutch government, i.e. taxpayers' money. Minister Bussemaker recently made 18.8 million euros available for the NOCI project, Netherlands Organ-on-Chip initiative, through the so-called 'Gravity program' of the NWO organization. The proposal for this project came about from the hDMT consortium, human Organ and Disease Model Technologies. hDMT is a foundation affiliated with MinacNed, the trade organization for micronano technology. See here the reason for a conversation with hDMT managing director and member of the Board of Directors of hDMT Janny van den Eijnden-van Raaij and a number of the scientists collaborating in the NOCI project. Christine Mummery, professor of developmental biology at the Leiden University Medical Center, speaks. She leads the NOCI project and also has an appointment as professor at the University of Twente. The other discussion partners are two professors known within FHI: Albert van den Berg, professor of sensor systems at the University of Twente and Lina Sarro, professor of microsystems technology at TU Delft. “As a biologist you have little idea what is possible with today's chip technology,” admits Christine Mummery. “It is a great experience for me to work with people like Lina and Albert. What we want is to gain more insight into diseases based on 'personalized medicine', i.e. the effect of substances in the body's own human cells. When I say 'we', it means Michel Ferrari, also professor in Leiden and specialized in brain disorders, Cisca Wijmenga, professor in Groningen, who mainly looks at intestinal diseases and Hans Clevers, professor of cell biology at the Hubrecht Institute in Utrecht. Thanks to Yamanaka's work, we can now grow nerve cells, heart cells, blood vessel cells and all kinds of other organs from stem cells. In the future, the technology could also be used for regenerative medicine, the regrowth of cells that are no longer there, but that is a long-term process for most conditions. We now first want to be able to put the cells that we grow on a chip so that we can administer substances via microfluidics and see how those cells then respond. You can then apply new medicines and therapies much faster and in a much more patient-specific manner, without the need for animal testing.”
“We became involved through the “Across Borders programme” of the KNAW, the Royal Dutch Academy of Sciences. Our role is to develop the systems and structures in microfluidics. If the cells enter a technological system, they must remain alive, arrive at the desired location correctly and the substances that need to be added must also arrive where the biologist wants them in the correct and controlled manner,” says Albert van den Berg. “In Delft we are again good at building 3D structures and sensors in a tiny integrated system in which you can see and measure what is happening,” is Lina Sarro's contribution. “Ronald Dekker, professor in Delft and also working for Philips, was already working with us on heart cells and flexible electronics and the collaboration came about through his contact with Christine. What Ronald does with stretching polymers to make roll-up chips for catheters turns out to be technology that is very suitable for Organ-on-Chip, although it requires different shapes. Delft's IC-like approach is important to be able to scale up later.” “You had very good technology, but so far you used it for the wrong cells for us. We had good cells, but used the wrong technology to conduct research on human tissues from stem cells,” Christine summarizes nicely. The research project proposal that has now been approved addresses the brain as well as the heart and intestines. “We want to make chips not only with brain cells as such, but we also want to look at the surrounding blood vessels and the like. We also want to do that with the heart and intestinal cells.” Mummery describes the ambitions. “We want to build a physiological model, including blood vessels. We want to look at the physical factors of tissue, for example when moving the heart or stretching.” She is talking about moving heart cells on a chip, as Ronald Dekker has shown several times at FHI conferences where he projected videos of them. “We want to see what a bacterium does during the peristaltic movement of an intestine. You need complex models for this with built-in sensors that can measure and monitor the reactions.” These are fascinating views or perhaps it would be better to speak of insights. “We also know that what the gut does can affect your mood. This goes through the brain and can then have an effect on the functioning of the heart. We want to investigate this by combining different chips into a system.” So it will not be a real body on a chip, but a number of chips that together form almost a complete body, in connection between the various organs. Janny van den Eijnden-van Raaij sees more projects within hDMT based on modeling the human body. “Food effects and cosmetics tests are also examined. In the US they immediately started talking about 'Body-on-a-Chip', but that is actually too pretentious.” She doesn't want to call it typical American window dressing. The NOCI project actually appears to be a subset of all initiatives within hDMT. “hDMT has all kinds of theme groups that define and implement different research programs,” we hear from Janny van den Eijnden-van Raaij. Christine Mummery mentions the 'Gut-on-a-Chip' project by Hans Bouwmeester at Wageningen University as an example. “That is part of NWO's 'Building Blocks of Life' programme.” Both Christine and Janny speak with pride about the recognition and slight jealousy within Europe. The recognition is evident from the fact that, at the initiative of hDMT, 'organ-on-chip' has now been included as a topic in several new H2020 work programs, including the EU 'FET Flagship' program, for Future and Emerging Technologies. This means that access to substantial European money is opened. “We have achieved that nicely. And there is already a relationship from NOCI to an EU project for drawing up a roadmap for Organ-on-Chip for which a proposal has been submitted.” What about corporate involvement? “Galapagos and GenMab participate within hDMT, in addition to the four TUs, four UMCs, two universities, the Hubrecht Institute and TNO,” reports Janny van den Eijnden-van Raaij. Albert van den Berg would like more smaller companies to be involved in the NOCI project. So far these have been parties such as Mimetas, Micronit, Ocello, Optics 11 and Pluriomics. According to Van den Berg, it could also be interesting for companies in the cosmetics and food industries. With hDMT, Janny would like to bring together a broad network group of companies via MinacNed with which matchmaking can be done for concrete projects. This does not necessarily have to be linked to participation as a partner in the hDMT consortium. “We would also like to monitor through such contacts whether we are doing what is needed.” The research as such is quite fundamental. Janny van den Eijnden-van Raaij reports that the American FDA, Food and Drug Administration, is now also considering Organ-on-Chip technology for drug testing. The pharmaceutical companies Emulate and Johnson & Johnson are also using the technology for testing in their product development. However, it should not be expected that a lot of new activity will arise in the short term based on the results of the research. The companies that start working on the technologies that 'enable' research will develop much more immediately. There is the economic and social benefit of fundamental research, both for the short and longer term. Organ-on-Chip will also be an important theme at the international MicroNano Conference on December 12 & 13 at the Beurs van Berlage in Amsterdam. This will be noticeable in the conference program as well as in the hands-on workshops, at the poster sessions and on the exhibition floor. It is also special that the annual MicroNano Bio Systems cluster workshop with European Commission Funded projects takes place this year during the MicroNano Conference. The European Commission has expressly asked hDMT to be present in this and that will happen.
Text: Kees Groeneveld/ Images: hDMT
“We became involved through the “Across Borders programme” of the KNAW, the Royal Dutch Academy of Sciences. Our role is to develop the systems and structures in microfluidics. If the cells enter a technological system, they must remain alive, arrive at the desired location correctly and the substances that need to be added must also arrive where the biologist wants them in the correct and controlled manner,” says Albert van den Berg. “In Delft we are again good at building 3D structures and sensors in a tiny integrated system in which you can see and measure what is happening,” is Lina Sarro's contribution. “Ronald Dekker, professor in Delft and also working for Philips, was already working with us on heart cells and flexible electronics and the collaboration came about through his contact with Christine. What Ronald does with stretching polymers to make roll-up chips for catheters turns out to be technology that is very suitable for Organ-on-Chip, although it requires different shapes. Delft's IC-like approach is important to be able to scale up later.” “You had very good technology, but so far you used it for the wrong cells for us. We had good cells, but used the wrong technology to conduct research on human tissues from stem cells,” Christine summarizes nicely. The research project proposal that has now been approved addresses the brain as well as the heart and intestines. “We want to make chips not only with brain cells as such, but we also want to look at the surrounding blood vessels and the like. We also want to do that with the heart and intestinal cells.” Mummery describes the ambitions. “We want to build a physiological model, including blood vessels. We want to look at the physical factors of tissue, for example when moving the heart or stretching.” She is talking about moving heart cells on a chip, as Ronald Dekker has shown several times at FHI conferences where he projected videos of them. “We want to see what a bacterium does during the peristaltic movement of an intestine. You need complex models for this with built-in sensors that can measure and monitor the reactions.” These are fascinating views or perhaps it would be better to speak of insights. “We also know that what the gut does can affect your mood. This goes through the brain and can then have an effect on the functioning of the heart. We want to investigate this by combining different chips into a system.” So it will not be a real body on a chip, but a number of chips that together form almost a complete body, in connection between the various organs. Janny van den Eijnden-van Raaij sees more projects within hDMT based on modeling the human body. “Food effects and cosmetics tests are also examined. In the US they immediately started talking about 'Body-on-a-Chip', but that is actually too pretentious.” She doesn't want to call it typical American window dressing. The NOCI project actually appears to be a subset of all initiatives within hDMT. “hDMT has all kinds of theme groups that define and implement different research programs,” we hear from Janny van den Eijnden-van Raaij. Christine Mummery mentions the 'Gut-on-a-Chip' project by Hans Bouwmeester at Wageningen University as an example. “That is part of NWO's 'Building Blocks of Life' programme.” Both Christine and Janny speak with pride about the recognition and slight jealousy within Europe. The recognition is evident from the fact that, at the initiative of hDMT, 'organ-on-chip' has now been included as a topic in several new H2020 work programs, including the EU 'FET Flagship' program, for Future and Emerging Technologies. This means that access to substantial European money is opened. “We have achieved that nicely. And there is already a relationship from NOCI to an EU project for drawing up a roadmap for Organ-on-Chip for which a proposal has been submitted.” What about corporate involvement? “Galapagos and GenMab participate within hDMT, in addition to the four TUs, four UMCs, two universities, the Hubrecht Institute and TNO,” reports Janny van den Eijnden-van Raaij. Albert van den Berg would like more smaller companies to be involved in the NOCI project. So far these have been parties such as Mimetas, Micronit, Ocello, Optics 11 and Pluriomics. According to Van den Berg, it could also be interesting for companies in the cosmetics and food industries. With hDMT, Janny would like to bring together a broad network group of companies via MinacNed with which matchmaking can be done for concrete projects. This does not necessarily have to be linked to participation as a partner in the hDMT consortium. “We would also like to monitor through such contacts whether we are doing what is needed.” The research as such is quite fundamental. Janny van den Eijnden-van Raaij reports that the American FDA, Food and Drug Administration, is now also considering Organ-on-Chip technology for drug testing. The pharmaceutical companies Emulate and Johnson & Johnson are also using the technology for testing in their product development. However, it should not be expected that a lot of new activity will arise in the short term based on the results of the research. The companies that start working on the technologies that 'enable' research will develop much more immediately. There is the economic and social benefit of fundamental research, both for the short and longer term. Organ-on-Chip will also be an important theme at the international MicroNano Conference on December 12 & 13 at the Beurs van Berlage in Amsterdam. This will be noticeable in the conference program as well as in the hands-on workshops, at the poster sessions and on the exhibition floor. It is also special that the annual MicroNano Bio Systems cluster workshop with European Commission Funded projects takes place this year during the MicroNano Conference. The European Commission has expressly asked hDMT to be present in this and that will happen.
Text: Kees Groeneveld/ Images: hDMT 
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