Complex Organoid Models for Drug Screening
Cells behave differently when they are cultured in 3D configuration, which is particularly important when evaluating their response to drugs and interventions. We are developing different 3D organoid models for different cell types to fully reflect their physiological response to specific drugs. These models can be used for improving the effectiveness of therapies in personalized medicine.
Apart from the 3D configuration, the native cancer microenvironment consists of multiple cell types such as stromal cells and immune cells other than cancer cells. These cells reside in an extracellular matrix in which they may remodel and interact with each other to bring about chemoresistance effects. We are working on complex multicellular models including liquid and solid tumors to mimic the 3D cancer microenvironment. For example, the 3D endosteal niche formed by mesenchymal stem cells (MSCs) for supporting the survival of acute myeloid leukemia (AML); neuroblastoma (NB) tumoroids with endothelial cell layer which we aim to model the metastatic activity of cancer cells; and airway epithelial model with multiple cell layers to mimic the air-liquid interface.
In normal tissues, the microenvironment would also influence cellular phenotype through physical, mechanical, and biochemical mechanisms. We have also developed several organoids such as the osteochondral tissue formed by osteogenic and chondrogenic differentiated MSCs and hair follicle models. Ultimately, we would like to apply these physiologically relevant models for personalized drug screening purposes.