A New Approach to Engineering Complex Organoids

A novel molecular engineering technology can precisely control the formation of organoids. Microbeads composed of precisely folded DNA are utilized to deliver growth factors or other signal molecules into tissue structures. This results in far more sophisticated organoids that closely resemble the individual tissues and have a more realistic cell mix than before.

The technique was developed by an interdisciplinary research team from the Cluster of Excellence "3D Matter Made to Order" at Heidelberg University, including researchers from the Centre for Organismal Studies and the Center for Molecular Biology, the university's BioQuant Center, and the Max Planck Institute for Medical Research in Heidelberg.

Organoids are tiny, organ-like tissue structures made from stem cells. They are employed in fundamental research to learn new things about human development or to examine disease progression.

Until now it was not possible to control the growth of such tissue structures from their interior. Using the novel technique, we can now determine precisely when and where in the growing tissue key developmental signals are released.”

Dr Cassian Afting, Physician Scientist, Centre for Organismal Studies

Tobias Walther is a Biotechnologist and Doctoral candidate at the Center for Molecular Biology of Heidelberg University (ZMBH) and the Max Planck Institute for Medical Research in Heidelberg.

The multidisciplinary research team of biologists, doctors, physicists, and materials scientists created microscopically tiny DNA beads that can be "loaded" with protein or other molecules.

These microbeads are implanted into the organoids and release their contents when exposed to UV light. This enables the release of growth factors or other signal molecules at any time and place in the growing tissue.

The researchers tried the procedure on retinal organoids from the Japanese rice fish medaka by carefully introducing microbeads containing a Wnt signal molecule into the tissue. For the first time, they were able to stimulate the formation of retinal pigment epithelial cells, the retina's outer layer, next to neural retinal tissue. Previously, adding Wnt to the culture medium would increase pigment cells while inhibiting neuronal retina growth.

Thanks to the localized release of signaling 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.”

Dr Kerstin Göpfrich, Professor and Researcher, Max Planck Institute

According to the researchers, DNA microbeads can be easily altered to convey a wide range of signal molecules in different types of cultivated tissue.

This opens up new possibilities for engineering organoids with improved cellular complexity and organization. More sophisticated organoid models could accelerate research on human development and disease and potentially lead to better organoid-based drug research.”

Dr Joachim Wittbrodt, Principal Investigator, Center for Organismal Studies, Heidelberg University

The new technology for producing more complicated organoids was developed at the "3D Matter Made to Order" Cluster of Excellence, which is run by Heidelberg University and the Karlsruhe Institute of Technology.

The research was financed by the European Research Council (ERC) through an ERC Starting Grant for Kerstin Göpfrich and the German Research Foundation. The study findings were reported in the journal "Nature Nanotechnology".

The German Research Foundation and the European Research Council (ERC) provided funding for the study under Kerstin Göpfrich's ERC Starting Grant. The research findings were published in the journal “Nature Nanotechnology.”