Organoids are miniature, organ-like tissue structures derived from stem cells. They have become a widely used tool in basic research, human disease modeling, and personalized medicine and have been established for various organs.
Until now, it has been impossible to control the growth of such tissue structures from their interior. However, a newly developed technique allows scientists to determine precisely when and where critical developmental signals are released in the growing tissue.
The interdisciplinary research team of biologists, physicians, physicists, and materials scientists developed a new molecular engineering technique that uses DNA microbeads to control the development of cultivated tissue. DNA microbeads release growth factors or signals inside tissue structures, creating more complex organoids that better mimic actual tissues and have a more realistic mix of cells.
These DNA microbeads can be “loaded” with proteins or other molecules. They are injected into the organoids and release their cargo when exposed to UV light. This allows the release of growth factors or other signal molecules within the developing tissue at any given time and location.
The scientists used microbeads with a Wnt signal molecule on the retinal organoids of the Japanese rice fish medaka. This allowed them to make retinal pigment cells form next to neural retina tissue for the first time. Previously, adding Wnt to the culture would only produce pigment cells and stop the growth of neural retina.
Prof. Dr. Kerstin Göpfrich, a researcher in synthetic biology at the ZMBH and the Max Planck Institute for Medical Research, said, “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.”
Scientists suggest that the DNA microbeads can be flexibly adapted to transport many different signal molecules in various types of cultivated tissue.
Prof. Dr Joachim Wittbrodt, who directed the research work with Prof. Göpfrich, said, “The DNA microbeads can be flexibly adapted to transport many different signal molecules in various 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.”
Journal Reference:
- Afting, C., Walther, T., Drozdowski, O.M. et al. DNA microbeads for spatiotemporally controlled morphogen release within organoids. Nat. Nanotechnol. (2024). DOI: 10.1038/s41565-024-01779-y
