Presenter: Shravanthi Rajasekar
Supervisor(s): Dr. Boyang Zhang
Project Description: Organoids which are miniaturized organs grown in lab from human stem cells have provided new opportunities to model biological processes and recapitulate organ development. However, organoid systems lack perfusable vascular networks to deliver nutrients and drugs. Their lack of vascularization and perfusion limit the capability of these models to recapitulate organ physiology effectively for drug testing or disease modelling. We have engineered a microfluidic platform, named IFlowPlate, using which we can culture up to 128 independently perfused and vascularized colon organoids in vitro. Unlike traditional microfluidic devices, our vascularized organoid-on-chip device with an open-well design does not require any external pumping systems and allows tissue extraction for downstream analyses, such as histochemistry or even in vivo transplantation. By optimizing both the ECM and the culture media formulation, we have co-cultured patient-derived colon organoids successfully within a self-assembled vascular network and found the colon organoids grow significantly better in our platform under constant perfusion vs. conventional static condition. Furthermore, we demonstrated a colon inflammation model with an innate immune function where circulating monocytes can be recruited from the vasculature, differentiate into macrophage and infiltrate the colon organoids in response to TNF-alpha inflammatory cytokine stimulation. With the ability to grow vascularized colon organoids under intra-vascular perfusion, our IFlowPlate platform could unlock new possibilities for screening potential therapeutic targets or modeling relevant diseases.