image: Endothelial network formation perfusing an organoid trapped in the microfluidic chip
Credit: CEA-Leti
In Vitro System Bypasses ‘Complex Technical Setups’ of Alternative Approaches And Supports Production Scaling
GRENOBLE, France – March 21, 2024 – The Interdisciplinary Research Institute of Grenoble (CEA-Irig), CEA-Leti and fellow European and Canadian institutes and researchers have demonstrated the complete vascularization of organoids on a microfluidic chip at speeds and flow rates similar to blood’s, improving functional maturation and enabling their long-term survival.
Organoids, which are a 3D assembly of self-organizing cells capable of partially mimicking different physiological characteristics of an organ or tissue, are proving to be highly useful for evaluating the therapeutic efficacy of drugs or new molecules. But they must be vascularized to promote the exchange and transport of nutrients and oxygen, otherwise their maturation and growth are impaired. In vivo, this vascularization is ensured by blood flow.
By vascularizing organoids in vitro and maintaining them in culture for 30 days in a microfluidic chip, researchers observed significant improvement in their growth, maturation and physiological functions, virtually equivalent to those observed after xenotransplantation in mice. This significant technological advance in organoid R&D also enables production scaling.
The breakthrough was reported in the February issue of Nature Communications in the paper, “A microfluidic platform integrating functional vascularized organoids-on-chip”.
“The development of vascular networks in microfluidic chips is crucial for the long-term culture of three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants,” the paper explains. “Despite rapid advancement in microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge in tissue engineering. Most existing microfluidic devices poorly reflect the complexity of in vivo flows and require complex technical set-ups.”
The team’s innovative idea was first to develop a self-organizing vascular network within the chip and then trap an organoid containing its own endothelial cells within it. Both networks are self-connected and they enabled the organoid to be perfused in vitro, mimicking the blood system.
“This work opens new avenues to understand biological mechanisms in much more relevant models of human origin, as well as for drug discovery and drug development of novel biological therapies,” said Xavier Gidrol, CEA-Irig scientist and project supervisor. “Organoids have now entered the field of personalized medicine, regenerative medicine and pharmacological research.”
“We have demonstrated a never-reported, improved functional maturation of the vascularized organoid-on-chip by using a reliable microfluidic chip made of thermoplastics, which are well-known in the plastic industries and compatible with production scaling in the near future,” said Fabrice Navarro, a CEA-Leti scientist and co-author of the paper.
The project included scientists and research engineers from France, Austria and Canada.
About CEA-Leti (France)
CEA-Leti, a technology research institute at CEA, is a global leader in miniaturization technologies enabling smart, energy-efficient and secure solutions for industry. Founded in 1967, CEA-Leti pioneers micro-& nanotechnologies, tailoring differentiating applicative solutions for global companies, SMEs and startups. CEA-Leti tackles critical challenges in healthcare, energy and digital migration. From sensors to data processing and computing solutions, CEA-Leti’s multidisciplinary teams deliver solid expertise, leveraging world-class pre-industrialization facilities. With a staff of more than 2,000 talents, a portfolio of 3,200 patents, 11,000 sq. meters of cleanroom space and a clear IP policy, the institute is based in Grenoble, France, and has offices in Silicon Valley, Brussels and Tokyo. CEA-Leti has launched 75 startups and is a member of the Carnot Institutes network. Follow us on www.leti-cea.com and @CEA_Leti.
Technological expertise
CEA has a key role in transferring scientific knowledge and innovation from research to industry. This high-level technological research is carried out in particular in electronic and integrated systems, from microscale to nanoscale. It has a wide range of industrial applications in the fields of transport, health, safety and telecommunications, contributing to the creation of high-quality and competitive products.
For more information: www.cea.fr/english
About CEA-Irig the Interdisciplinary Research Institute of Grenoble (France)
CEA-Irig is a fundamental research institute at CEA that employs 1,100 people. Based in Grenoble, France, the institute covers a wide range of theoretical and experimental research in the fields of physics, chemistry, biology and instrumentation. The teams associated with other French research institutes are involved in 4 major thematic pillars: Biology-Health, Physics-Digital, Energy-Environment and Cryotechnologies. All of its R&D is supported by the exceptional research platforms with instruments at the cutting edge. Some of these are National Research Infrastructures serving the French and European communities, with the French light and neutron lines at ESRF and ILL (F-CRG: French Collaborative Research Group). The CEA-Irig is a "knowledge factory" and a place of innovation to support societal transitions (digital, health and energy).
For more information: https://irig.cea.fr/drf/irig/english
Press Contact
Agency
Sarah-Lyle Dampoux
+33 6 74 93 23 47
Journal
Nature Communications
Method of Research
Experimental study
Subject of Research
Not applicable
Article Title
A microfluidic platform integrating functional vascularized organoids-on-chip
Article Publication Date
16-Feb-2024