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bioRxiv · 10.1101/2025.07.09.663178

Derivation of cardiomyocyte-propelled motile aggregates from stem cells

Ho, C.·Glykofrydis, F.·Godage, G.·Poon, K.·Kunnan, M.·Swedlund, B.·Murillo, S.·Morsut, L.
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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.

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Ho, C., Glykofrydis, F., Godage, G., Poon, K., Kunnan, M., Swedlund, B., Murillo, S., Morsut, L.. 2025-07-09. Derivation of cardiomyocyte-propelled motile aggregates from stem cells. https://doi.org/10.1101/2025.07.09.663178

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