Giving rise to more complex organoids with microbeads

Researchers at Heidelberg University and the Max Planck Institute for Medical Research have used a novel molecular engineering technique to influence the growth of organoids using microbeads, which gives rise to more complex organoids. This was developed in the Cluster of Excellence ‘3D Matter Made to Order’, which is jointly operated by Heidelberg University and the Karlsruhe Institute of Technology.

Microbeads, constructed from specifically folded DNA, can be loaded with proteins or other molecules. Once injected into the organoids, the microbeads’ contents are released upon exposure to UV light. This enables the release of growth factors or other signal molecules at any given time and location in the tissue. Dr Cassian Afting, physician scientist at the Center for Organismal Studies (COS) at Heidelberg University commented: “Until now it wasn’t possible to control the growth of such tissue structures from their interior.”

Retinal organoids of Japanese rice fish medaka were used to test this process. The team inserted microbeads loaded with a Wnt signal molecule into the tissue. This allowed them, for the first time, to induce retinal pigment epithelial cells to form adjacent to neural retinal tissue.

Previously, adding Wnt to the culture media would induce pigment cells but suppress neural retina development. Dr Kerstin Göpfrich, synthetic biology researcher at The Center for Molecular Biology of Heidelberg University, explained: “Thanks to the localised release of signalling molecules, we were able to achieve a more realistic mix of cell types, thereby more closely mimicking the natural cell composition of the fish eye than with conventional cell cultures.”

The DNA microbeads can be adapted to transport numerous different signal molecules in various types of cultivated tissue. “This opens up new possibilities for engineering organoids with improved cellular complexity and organisation,” stated Dr Joachim Wittbrodt, Heidelberg University, who directed the research work together with Dr Göpfrich.

This study was published in Nature Nanotechnology.