A new molecular engineering technique has been developed that can precisely control the development of organoids. Published in Nature Nanotechnology, This innovative approach uses microbeads made of specially folded DNA to release growth factors or signaling molecules within the tissue structures. The result is the creation of more complex organoids that more closely mimic real tissues, offering a more accurate mix of cell types than previously possible. This technique was developed by an interdisciplinary team from the Cluster of Excellence “3D Matter Made to Order,” and includes researchers from the Centre for Organismal Studies, the Center for Molecular Biology of Heidelberg University, the BioQuant Center, and the Max Planck Institute for Medical Research in Heidelberg.

Organoids are small, organ-like tissue structures derived from stem cells and are widely used in research to study human development and diseases. “Until now, it wasn’t possible to control the growth of such tissue structures from their interior,” says Dr. Cassian Afting, a Physician Scientist at the Centre for Organismal Studies (COS). “Using the novel technique, we can now determine precisely when and where in the growing tissue key developmental signals are released,” adds Tobias Walther, a biotechnologist and doctoral candidate at the Center for Molecular Biology of Heidelberg University (ZMBH) and the Max Planck Institute for Medical Research.

The team, composed of experts from various fields, designed microscopically small beads of DNA that can carry proteins or other molecules. These microbeads are inserted into the organoids and can release their contents when triggered by UV light, allowing researchers to control the timing and location of the release of growth factors or signaling molecules during tissue development.

The researchers tested this technique on retinal organoids from the Japanese rice fish medaka. They introduced microbeads containing a Wnt signal molecule into the tissue, successfully inducing retinal pigment epithelial cells to form alongside neural retinal tissue. Previously, adding Wnt to the culture media would result in the formation of pigment cells but suppress neural retina development. “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,” explains Prof. Dr. Kerstin Göpfrich, a researcher in synthetic biology at the ZMBH and the Max Planck Institute for Medical Research.

The DNA microbeads can be adapted to deliver a variety of signaling molecules across different types of tissues. “This opens up new possibilities for engineering organoids with improved cellular complexity and organization,” says Prof. Dr. Joachim Wittbrodt, who co-led the research with Prof. Göpfrich. “More sophisticated organoid models could accelerate research on human development and disease and potentially lead to better organoid-based drug research,” adds Prof. Wittbrodt, a developmental biologist from the COS.