Motile Living Biobots Self-Construct from Adult Human Somatic Progenitor Seed Cells

Fundamental knowledge gaps exist with respect to the plasticity of cells from adult soma and the potential diversity of body shape and behavior in living constructs derived from such genetically wild-type cells. Here we introduce Anthrobots, a spheroid-shaped multicellular biological robot platform with diameters ranging from 30 to 500 microns. Anthrobots have an inherent capacity for motility in aqueous environments, via cilia covering their surface. Each Anthrobot starts out as a single cell, derived from the adult human lung, and self-construct into a multicellular motile biological machine after having been cultured in extra cellular matrix for 2 weeks, followed by a transfer into a minimally viscous and adhesive habitat. Anthrobots exhibit a wide range of behaviors with motility patterns ranging from tight loops to straight lines with speeds ranging from 5-50 microns/second. Our anatomical investigations reveal that this diversity in their movement types is significantly correlated with their diversity in morphological types. Anthrobots can assume diverse morphologies from fully polarized to wholly ciliated bodies with spherical or ellipsoidal shapes, each correlating with a distinct movement type. Anthrobots were found to be able to traverse live human tissues in various ways as a function of these different movement types. Remarkably, Anthrobots are shown to be able to induce rapid repair of wounds in human neural cell sheets in vitro. By controlling microenvironmental cues, entirely novel structure, behavior, and biomedically-relevant capabilities can be discovered in morphogenetic processes not requiring direct genetic manipulation. Highlights This work is part of the existing science of organoids and synthetic bioengineering Anthrobots are made from discarded tracheal epithelial (skin) cells of adult patients The cells self-organize, in a dish, into tiny clusters of cells that swim around by waving cilia (which other animals use, and the human trachea uses to propel particles out of the airway) They are related to Xenobots, showing that the Xenobot phenomenon is not due to special features of embryonic or of amphibian cells – adult human cells do it too, which suggests this is a wide-spread cellular capability No transgenes were used – their abilities are completely natural Biobots are a platform for learning about native cellular intelligence, and showing how life explores new ways of being (cellular creativity, competency, plasticity) Anthrobots can heal wounds in neural tissue; it is not known yet what other surprising behaviors and capabilities they may have Potential future positive impacts and uses – bio-robotics for regenerative medicine: ○ Chasing down cancer cells in your gut ○ Putting down pro-regenerative drugs or other molecules ○ Out of the body sculpting engineered tissue for transplantation ○ Patient-specific avatars for drug testing = personalized medicine (reduces animal testing use, while showing you effects of drugs on your own tissues) Safety aspects ○ Made of patient’s own cells - no problem with immune rejection and no need for immune suppressing medication ○ Limited life span – they only live a few weeks ○ Biodegradable ○ Very stringent survival requirements – they can’t live outside of a very specific lab culture environment (unlike all the artificial bacteria and viruses made today) ○ They do not reproduce ○ Not genetically-modified Ethics ○ No embryonic cells used, so no human (and no animal) was negatively impacted ○ Skin only, so concern for their welfare should be much less than for brainy experimental or food animals like fish or cows ○ We view this as a new tool with which to advance the moral responsibility to actively reduce human and animal suffering from biomedical causes