Abstract

Modeling the Embryonic Neural Tube in a Chip

Thomas Laurell, Professor, Lund University

Studying the biology of the early embryonic development stages of the human brain poses severe challenges in terms of access to fetal brain tissue. Current strategies are either referred to studies on animal models or so called neurospheres organoids. Although more widely available, current animal models do not fully reflect the human biology, neither in terms of brain size nor in anatomy. Neural organoids (spheroids), on the other hand, can be generated in large quantities but with the draw back that the organization of the brain regions occurs randomly, in contrast to the spatially well-structured organization along the rostro caudal axis of the fetal brain, in the fore brain, midbrain and hind brain regions. To overcome these bottlenecks, we have developed an organ-on-a-chip (OOC) system that reproducibly generates a neural tissue from human embryonic stem cells with a rostro caudal organization modelling the human embryonic brain. A core of this organ-on-chip system is a gradient generator that produces a morphogen (gsk3i) gradient across the cell culture during the initial neural stem cell patterning phase. The obtained rostro caudal organization has been verified by RNA expression profiling of region specific genes and this OOC platform now provides a robust and reproducible platform to model the human fetal brain. The OOC-system design and performance will be presented and the outlook towards new opportunities to accomplish temporally resolved monitoring of cellular signaling in the course of brain development will be discussed.