New models to study tissue homeostasis and tumorigenesis

Understanding of mammalian biology at the tissue level and studying organ development and how they change during disease state in humans has been difficult due to ethical concerns and inaccessibility of sample. Conventional monolayer cell cultures, derived from human tissue have been used for decades to create experimental tools to study basic and cancer biology. Unfortunately, these cell lines are transformed and acquire irrelevant mutations overtime that do not reflect the biological characteristics of the tissue of origin. Moreover, these cultures are two-dimensional and do not mimic the tissue architecture and the cellular heterogeneity present in the tissue or the tumor of origin. An alternative to model cancer has been to put human tumors growing into mice creating ‘’patient-derived xenograft’’ but the absence of the immune system in these models and the cross-species difference between human tumor cells and the mouse environment has limitation in the interpretation of the results. Furthermore, these models are expensive and time-consuming.

Advances in developmental and stem cell biology has allowed to decipher the growth factors and signaling pathways necessary for a stem cell to receive proper environmental conditions to differentiate and arrange themselves to form a mini-organ in vitro. These three-dimensional (3D) structures called ‘’organoids’’ display similar functional properties of the tissue of origin including the genetic and the cellular heterogeneity, making them highly valuable tools to study tissue homeostasis and tumorigenesis.

Developing platforms or centers that create organoids on demand allow researchers to study biology closer to physiological conditions and it contributes toward personalized medicine. These platforms represent a first-in-class physiological platform for research on living disease tissue.