Derivation of cardiomyocyte-propelled motile aggregates from stem cells.
Publication Year:
2025
PubMed ID:
40672161
Funding Grants:
Public Summary:
Robots often take inspiration from how animals move, but animals build themselves through natural developmental processes, unlike machines assembled part by part. Scientists are now exploring whether stem cells can self-organize into tiny, muscle-powered “biobots.” In this study, researchers showed that certain stem cell protocols can create small beating cell clusters, but the results were inconsistent. They developed a new method that reliably produces larger, more strongly contracting cell aggregates by guiding the cells through specific developmental steps. These clusters can move on their own, and added cues help control where the contractions occur. This work brings scientists closer to creating autonomous, self-assembled biological robots and offers a new way to study how muscle-based movement and heart development evolved.
Scientific Abstract:
Robotics draws inspiration from biology, particularly animal locomotion based on muscle-driven contractions. While traditional engineering assembles components sequentially, locomotive animals are built via self-organized developmental programs. Stem cells, under the right conditions, can mimic these processes in vitro, offering a pathway to develop muscle-propelled biobots in a self-organized building process. Here, we demonstrate that existent cardiogenic gastruloid protocols can produce motile aggregates from mouse embryonic stem cells, although with very limited efficiency. We then identify a novel protocol that yields contractile aggregates with higher frequency and larger contractile areas. In this novel protocol, mesendoderm induction using TGF-beta ligands is followed by cardiogenic induction with FGFs and VEGF. Synthetic organizers further control contraction localization. Aggregates developed via this protocol show enhanced motility, marking a step forward towards building motile cardiobots from self-organized biological material. This strategy opens new possibilities for designing autonomous biobots and studying the evolution of muscle-powered movement of multicellular organisms and cardiovascular development.