A recent advancement in molecular engineering allows for precise control over the growth of organoids. This method utilizes microbeads crafted from specifically folded DNA to release essential growth factors and signaling molecules within tissue structures. Consequently, the resulting organoids are significantly more intricate, better at mimicking actual tissues, and exhibit a more accurate cellular composition compared to previous models.
A recent advancement in molecular engineering allows for precise control over the growth of organoids. This method utilizes microbeads crafted from specifically folded DNA to release essential growth factors and signaling molecules within tissue structures. Consequently, the resulting organoids are significantly more intricate, better at mimicking actual tissues, and exhibit a more accurate cellular composition compared to previous models. An interdisciplinary research team from the Cluster of Excellence “3D Matter Made to Order” involving researchers at the Centre for Organismal Studies, the Center for Molecular Biology of Heidelberg University, the university’s BioQuant Center, and the Max Planck Institute for Medical Research in Heidelberg created this innovative technique.
Organoids are small, organ-like structures made from stem cells that resemble actual tissues. They are valuable in fundamental research for gaining insights into human development and investigating disease progressions. According to Dr. Cassian Afting, a Physician Scientist at the Centre for Organismal Studies (COS), “Previously, it was impossible to manage the internal growth of these tissue structures.” Biotechnologist Tobias Walther, a doctoral student at the Center for Molecular Biology of Heidelberg University (ZMBH) and the Max Planck Institute for Medical Research, adds, “With our new technique, we can accurately control when and where critical developmental signals are released within the expanding tissue.”
The collaborative team of biologists, physicians, physicists, and materials scientists developed tiny DNA beads capable of carrying proteins or other molecules. These microbeads are introduced into the organoids and release their contents upon exposure to UV light. This method allows for the controlled release of growth factors and other signaling molecules at specific times and places within the developing tissue.
The researchers experimented with retinal organoids from the Japanese rice fish medaka by carefully inserting microbeads containing a Wnt signaling molecule into the tissue. This marked the first occasion where they could encourage retinal pigment epithelial cells, which form the outer layer of the retina, to develop alongside neural retinal tissue. Previously, adding Wnt to the culture medium would promote pigment cell formation but inhibit neural retina growth. Prof. Dr. Kerstin Göpfrich, a synthetic biology researcher at the ZMBH and the Max Planck Institute for Medical Research, explains, “The targeted release of signaling molecules enabled us to achieve a more accurate mix of cell types, closely resembling the natural cellular composition found in the fish eye compared to traditional cell cultures.”
According to the researchers, the DNA microbeads can be easily modified to transport a variety of signaling molecules across different cultivated tissues. Prof. Dr. Joachim Wittbrodt, who co-led the research with Prof. Göpfrich, states, “This unlocks new avenues for engineering organoids with greater cellular complexity and organization.” He further notes that advanced organoid models could enhance research into human development and diseases, possibly improving organoid-based drug discovery.
This new method for crafting more complex organoids was developed within the Cluster of Excellence “3D Matter Made to Order,” a joint initiative by Heidelberg University and the Karlsruhe Institute of Technology. The research was supported by the European Research Council (ERC) through an ERC Starting Grant awarded to Kerstin Göpfrich, along with funding from the German Research Foundation. The findings were published in the journal Nature Nanotechnology.
