Descripción del proyecto
Técnicas avanzadas de ingeniería de organoides para impulsar la investigación de enfermedades y el desarrollo de fármacos
Los organoides cerebrales son estructuras autoensambladas en tres dimensiones derivadas de células madre pluripotentes inducidas humanas, que reproducen tanto la estructura como la función del cerebro fetal humano. Los organoides podrían sustituir a los actuales cultivos celulares bidimensionales «in vivo» y a los modelos animales con fines de diagnóstico y tratamiento, pero esto aún no se ha hecho realidad debido a la falta de métodos de preparación adecuados. El objetivo del proyecto PHOENIX, financiado con fondos europeos, es crear un proceso de ingeniería de organoides perfecto para investigar la reproducibilidad, la maduración controlada y la vascularización de los organoides cerebrales. Mediante acustoforesis, un método de manipulación de partículas y células por ultrasonidos, los investigadores tratarán de lograr la encapsulación ordenada de células madre en gotículas de hidrogel. También crearán una plataforma microfluídica en la que las células se diferenciarán en condiciones totalmente controladas.
Objetivo
The aim of PHOENIX is to use my expertise in microsystems engineering to close critical technology gaps in organoid generation. Cerebral organoids are 3D self-assembled structures derived from human induced pluripotent stem cells, replicating both structure and function of the human foetal brain. Organoids have the potential to replace existing 2D cell cultures and animal models, but this has not yet been realised due to rudimentary preparation methods.
In PHOENIX, three important technology gaps will be addressed: reproducibility, controlled maturation and vascularisation. I aim to build on my pioneering research on droplet acoustofluidics and the scientific output of my ERC Starting Grant to develop three microfluidic modules that at the end of the project shall be integrated into a seamless organoid engineering pipeline. The technology in focus is acoustophoresis, a method to manipulate particles and cells by ultrasound. This will be used to achieve ordered encapsulation of stem cells in hydrogel droplets and develop a microfluidic platform where the cells can be differentiated under fully controlled conditions. Finally, two-photon writing will be used to integrate a vascular network with the organoid constructs to form an important delivery architecture for nutrients and blood components. PHOENIX will be focused on both technology development and thorough biological characterisation of the resulting organoids to demonstrate both expected, and unexpected, benefits of transferring organoid generation on-chip.
Collaborations have been established with Prof. Christine Mummery and Dr. Valeria Orlova, both at LUMC, NL as well as Dr. Anna Falk at KI, SE to provide expertise in complementary fields of this highly interdisciplinary project. The expected output of PHOENIX is a microfluidic technology that enables high-throughput generation of cerebral organoid with a multi-regional structure and vascularisation in a direct process.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitución de acogida
751 05 Uppsala
Suecia