Establishment of Brain Organoids from Rats

In the years 1983-87, I developed a brain organoid cell culture system where fetal rat brain cells are assembled into 3-dimensional structures as spheroids. Through a number of publications we showed that the immature brain cells, within these spheroids, differentiated into organotypic brain structures containing mature neurons, oligodendrocytes and astrocytes. We also showed that these organoids contain myelinated axons, synaptic complexes and a complex neuropil. Thus these organdies contain all the main cell components as found in the adult brain. During the period 1990-2000, we confronted these brain organoids with tumor spheroids obtained from patients with malignant brain tumors and we were able to follow, in vitro, how the tumor cells invade into the normal brain. This work led to a high number of publications an several doctoral projects. From 2000 and on, we started to use, much more nude rats to determine mechanisms of tumor cell growth and progression. With the advent of new gene and imaging technologies, we now believe we have the capacity to make a new and better utilization of our in vitro co-culture system, -in particular in order to unravel mechanisms related to tumor cell invasion. We believe that by implementing the brain organoid system today will significantly reduce the number of animals used. Also, the proposed project is closely in line with the concept of "reduction, refinement and replacement" in animal research