Description
An organoid is a miniature three-dimensional biological structure that mimics certain functions of an organ, though not all. Pluripotent stem cells which can multiply almost indefinitely and differentiate into various types of specialised cells or adult stem cells are used to create organoids. These cells are cultured in vitro under specific conditions promoting their differentiation and spatial organisation, thus mimicking the development of cells in an embryo or adult tissues capable of self-regeneration. Embryonic Stem Cells (ESCs) or Induced Pluripotent Stem Cells (IPSCs) can make brain and spinal organoids. Indeed, these cells can be differentiated into neural cells, thanks to knowledge of how neural cells are specified in vivo. Despite progress, current in vitro models cannot fully replicate the complex cellular diversity and spatial organisation in the nervous system, such as the brain or spinal cord. This limitation restricts their effectiveness in biomedical applications.
Inspired by tissue patterning mechanisms during early brain embryonic development, we designed and microfabricated a device that enables localized delivery of morphogens to human embryonic stem cell (hESC) colonies to generate spatially patterned brain and spinal organoids. The device allows precise control over the position, size, and timing of morphogen exposure while preserving standard culture conditions. Cell dynamics and fate specification were analysed using live imaging and immunostaining.
I will present proof of concept of localized stimulation of tissues by our microfabricated devices using BMP stimulation of hESC as a benchmark assay. Functional validation showed that cells exposed to BMP4 patches specifically responded to the signal, as shown by localized pathway activation and changes in cell identity, while surrounding regions remained unstimulated. These results confirm that the device enables precise spatial control of morphogen delivery and effective basal signal reception by pluripotent cells. In the future, combining this approach with micropatterning and differentiation protocols will allow the controlled generation of spatially organised organoids.