Anthrobots: motile organoids made of human cells for clinical therapeutic purposes

What are Anthrobots[TM]?

Earlier reports of tiny biological “Xenobots[TM]” made from assembled frog cells captured media attention and the fascination of the public, as these lab-made organisms could crawl around a Petri dish, work together to collect piles of debris, and even make copies of themselves for a limited number of cycles. Anthrobots are similar in nature, but this time, they have been made from human cells. Specifically, they are made from epithelial, or skin cells from the lining of the tracheal tube of adult patients. Like all skin cells in the body, they are naturally discarded and replaced all the time. More importantly, Anthrobots are a new platform for uncovering latent capabilities (such as driving tissue repair) of patients’ own unmodified cells.

Why are researchers now using human cells to make the bots?

In order for biobots to do something useful in a clinical context – such as clearing out clogged arteries, or delivering drugs to tumors or wounds, it would be necessary to make them using the patient’s own cells to prevent the bots from triggering an immune response - immune suppressants would not be needed. Using adult human cells – without genetic modification -  opens up a new area of exploration to find their hidden capabilities in a different context. For example, we would not have expected that tracheal skin cells constructed into Anthrobots could encourage growth of neural tissue, but that is exactly what they did.

How are the Anthrobots[TM] made?

The bots actually self-assemble in a lab dish into tiny clusters resembling “organoids.” The self-assembly is helped along by a cell culture process, growing them in a liquid and nutrient environment that is conducive to their taking a desired shape. Anthrobots swim around by waving little hairs on their surface called “cilia”. This is why the researchers used the mucosal skin cells from the trachea. In the body, the normal function of the cilia is to help clear the airways by carrying excess mucus and other unwanted fine particles back to the mouth where it can be swallowed or discarded. When assembled into the Anthrobots, the cilia act like a propulsion system to enable them to move on their own.

What is the significance of AnthrobotsTM, outside of their potential future therapeutic uses?

Anthrobots and their predecessor Xenobots reveal that normal body cells, with no new DNA or other modifications, can assemble into novel forms and exhibit new and interesting behaviors. Learning how cells behave in a novel arrangement, including the ability to communicate with other cells in the group, and initiating healing when the bot is damaged, tells us how healing, regeneration, and cell and tissue organization work in the original body – frog or human.

Much of modern bioengineering is focused on manipulating the genomic hardware of the cell. Creating biobots focuses on the “software” – how the cells are arranged together, and how they communicate with each other to generate new behaviors and functions.

An analogy might be the popular engineering toy LEGO MINDSTORMS® which is a toolset of many different shapes and kinds of blocks. Some blocks have sensors, some have mechanical parts to create movement, and some have onboard computers. The cells of a Xenobot or Anthrobot also contain biological sensors, mechanical parts, the ability to process information, and much more. Those cells, like the LEGO MINDSTORMS® parts, can be combined to create a limitless combination of robots with different capabilities.

Anthrobots are related to the field of organoid research – which creates tiny versions of full-size organs to study how the organs work and to screen new drugs. Anthrobots are also organoids, except that they have a shape, function and behaviors different from the original tissue from which they derive - they are not just a simplified version of a full-sized organ.

What can AnthrobotsTM do, and what might they do in the future?

Much like Xenobots, Anthrobots can move about in laboratory dish. Remarkably, the researchers demonstrated that Anthrobots are capable of healing scratches in human peripheral neural tissue in vitro. This is a promising start, suggesting that many potential capabilities of Anthrobots remain to be discovered. It evokes a future when Anthrobots could do much more as a therapeutic tool:

·         Chasing down and destroying cancer cells in the gut

·         Releasing drugs and factors that aid in regeneration in parts of the body damaged by injury or disease

·         Clearing arteries of atherosclerotic plaques

·         Helping to create engineered tissue in a lab environment, which could then be transplanted into a patient

·         Being used as patient specific ‘avatars’ for drug testing, showing the effects of a drug on the patient’s own tissues, in a lab setting, and reducing the need for animal testing.

They look like living organisms – are they safe to use? Can they run out of control?

Anthrobots are inherently a very safe technology. Although they move about like tiny micro-organisms, they are more like tiny organoids, or clusters of cells that have the added capability of movement. They lack a critical component of a true micro-organism in that they cannot replicate on their own. Even Xenobots, which have the capability to make copies of themselves for a few cycles, cannot do so without human assistance.

Anthrobots have a limited life span and remain viable for only a few weeks. These collections of skin cells cannot survive outside the nutrient rich environment provided in the lab. This is much safer than most of the bioengineered bacteria and viruses commonly used and contained in laboratory research which are capable of replicating and surviving outside the lab.

Anthrobots are biodegradable, so if used in a therapeutic context, they ultimately break down in the body to natural components after they have finished their task

The creation of this new tool carries on a tradition in medical science of harnessing human cells to carry out therapeutic and healing tasks. This includes:

·         Enlisting the action of B cells moving about the immune system to fight a disease using vaccines.

·         Replacing marrow cells by transplant from another patient to help restore a patient’s immune system.

·         All of transplantation medicine, from corneas to coronary arteries, where human cells organized into tissue or organs are enlisted to help restore a patient to health.

Anthrobots, an assembly of human cells, opens the possibilities of designing and engineering behaviorally-rich organoids that move and carry out entirely novel functions.

What principles guide the ethical conduct of this research using human cells?

·         No embryonic cells are used in creating the bots, and cells are obtained by biopsy or less invasive means from patients who have given their consent that the cells can be used for this research. No humans or other animals are negatively impacted in obtaining the source material.

·         The bots in this research use epithelial, or skin cells only. There is no neural component and no brain.

·         The bots are constructed so that they are created, controlled and carry out their function in the lab or ultimately as a human therapeutic tool.

·         According to the researchers: “We have a positive moral responsibility to actively reduce human and animal suffering from pervasive biomedical problems and unmet health needs world-wide. This is a new tool with which to eventually improve life for everyone.”