In the last two decades, three-dimensional (3D) cell culture has become a central laboratory method. Across laboratories and institutes, researchers use 3D cell culture to answer questions about how tissues form, function, and repair themselves.
While many tissue engineering strategies have struggled to generate complex tissue models, a more effective approach builds on the natural ability of stem cells to self-organize. With the right, well-defined signals, stem cells can form multicellular patterns, compartments, and functional circuits that more closely resemble what they do in the body. The rise of organoids reflects this conceptual and practical shift. Organoids are miniature, simplified organ-like tissues grown from stem cells in the lab that mimic key features of real organs. They can contain highly functional cell types and broaden the range of cell types that can be generated and maintained in the lab, including types that were previously hard to obtain. Yet organoids often develop variable, hard-to-predict structures at larger scales. Contributing factors include poorly defined matrices and culture conditions, which still lack the local and time-sensitive control seen in embryonic development.
A new generation of lab-grown models could help close these gaps by following developmental paths more closely. Stem cell-derived embryo models show that shape and function can arise together in a tightly linked way, reflecting key morphological changes during early development. So far, these models mainly capture only the earliest developmental stages, but the Morphogenetic Micro Engineering team at the MERLN Institute aims to extend them to learn more about organogenesis, the formation of organs. If bioengineered tissues can be guided through key developmental milestones in the lab, it may be possible to generate physiologically relevant tissue analogues with structures that more accurately reflect early organ development.
Reaching this goal would open major opportunities. It would enable functional and anatomically accurate multicellular models for studying human development, organ formation, and regeneration. The role of environmental factors in causing congenital malformations could be investigated systematically, and tissues that are both functionally mature and anatomically correct could eventually be engineered for transplantation.
To get there, cell culture systems must improve substantially. We need new tools that guide stem cells with precise control over space and time, similar to the complex and fast-changing environment of developing tissues in a living organism. Our work focuses on developing such innovative cell culture tools that allow advanced 3D cell culture models to move through key morphological events step by step. Together, these capabilities create conditions where in vitro morphogenesis becomes something we can reliably design for. This will be a key step in connecting stem cell-derived embryo models with regenerative medicine.
Achieving this goal requires a multidisciplinary effort spanning stem cell biology, developmental biology, bioengineering, physics, computation, and clinical science. DRIVE-RM is a consortium built for this moment. Its cross-disciplinary structure and shared infrastructure support progress on problems that single laboratories cannot solve alone.
The age of 3D cell culture has shown what becomes possible when we work with biological complexity rather than avoiding it. The coming age of in vitro morphogenesis will be defined by systems that reproduce the coordinated “dance” of development and deliver the right signals in a changing spatial and temporal context to generate functional tissues with complex structures.
