לוח שנה משולב

iPS-derived cells, primary cells and even immortal cell lines grown in standard 2D culture conditions are valuable tools for basic research, drug discovery and drug safety. However, the selection and detection of active compounds based on such in vitro models has so far been of limited value. Two major limitations could explain this phenomenon. First, monolayer cells do not reflect properly native tissue morphology and second, available relevant readouts are limited. Consequently, there is increasing awareness that the development of cellular models with higher physiological relevance coupled to more informative readouts are prerequisite to improving cell-based assays.

In this context, we have developed several models based on micropattern technology as well as dedicated image analysis that address individually or simultaneously the bottlenecks cited above. Examples of the different applications will be presented with a specific highlight on multi-cellular models where several key cellular features demonstrated higher maturation levels on micropattern compared to conventional 2D cultures. The apparent resuscitation and/or stabilization of cellular functions allowed implementation of innovative readouts that are more relevant to the physiology of the systems, using imaging and High Content Analysis. Furthermore, the micropatterned organ models consist of multiple homogeneous uniform structures per well, facilitating segmentation and identification of features such as width of myotubes for higher throughput automated image analysis.

Alltogether, our work suggests that control of cell adhesion and cell-cell interactions promotes multi-cellular self-organization and enhances overall function, opening up access to novel cellular readouts. Micropatterns offer an opportunity to improve upon 2D cultures of several cellular models, even for cells that are the closest representatives of in vivo functionalities, further upgrading their usefulness for screening and mechanistic investigation of candidate drugs or signaling pathways.