Devangshu Datta: Springing a stem-cell surprise

Human tissues can repair a damaged heart - this and other stunning discoveries can lead to useful biological inventions

Engineers have always derived inspiration from nature. Aircraft mimic birds with streamlined bodies and wings to optimise lift and lower resistance. Jet propulsion exploits Newton’s Third Law (“Every action causes an equal and opposite reaction”) by expelling gases backwards to move an aircraft forward. It also has natural parallels. Squids and octopi use the Third Law to move around at speeds of up to 40 kilometres an hour by squirting water. A mechanical pump mimics the action of the heart, by moving liquids around under pressure.

Bioengineering takes things one step further by marrying biological blueprints with biological materials. Bioengineers use organic materials like living cell tissue rather than metals, plastic or fibreglass.

 

A collaborative project between the California Institute of Technology (Caltech) and the Wyss Institute for Biologically Inspired Engineering at Harvard University has just created an artificial jellyfish. It looks and swims like a jellyfish, but it’s built out of the heart muscle cells of a rat.

The pseudo-organism has been named “medusoid”. Jellyfish are called medusa because their poisonous tendrils look like the snaky hair on the head of the Greek Gorgon of legend. The medusoid isn’t just a proof of concept in re-engineering a complex biological organism; it provides vital insights into heart action.

The medusoid is just under 1 centimetre in diameter at rest. It has eight appendages. When it’s hit by an electrical current, these legs contract and curl together, pushing the body up to form a dome. Water is trapped under the dome. As the muscles relax, the water is pumped out, using Newton’s Third Law to move.

This mimics the action of a live jellyfish, which also pumps water by curling and uncurling legs. The jellyfish eats as it moves — the pumping creates vortices that throw water into its mouth. The natural jellyfish has a tiny pacemaker that co-ordinates muscle contraction by electrical impulses.

One of the project team leaders, Kevin Kit Parker, is an applied physicist at the Wyss Institute. His specialisation is cardiovascular action. He felt cardiac research was running into a bottleneck because researchers lacked insights into the way biological pumps worked. Heart drugs can only be initially tested in the lab for the contracting effect on tissue culture in dishes. Nobody has a holistic view of the effect of a drug on the pumping mechanism.

In 2007, Parker was visiting the New England Aquarium in Boston. He noticed that jellyfish swim by pumping muscles in much the same way the human heart works. He wondered whether studying jellyfish could provide insights. He also thought that it might be possible to construct an artificial jellyfish using living tissue.

In early 2008, John Daibiri, a fluid mechanics specialist from Caltech was visiting Wyss. Parker and Daibiri got together and decided to build an artificial jellyfish. They studied a specific species, Aurelia Aurita (the moon jellyfish).

Along with several assistants, they used a series of computer programs to map exactly how jellyfish muscles worked. They adapted a law enforcement fingerprint recognition program, staining proteins to analyse the internal protein network pattern at cellular level. Parker’s hunch proved correct. Jellyfish muscles work exactly the same way as the human heart with electrical impulses co-ordinating contractions.

When the team understood the physics of jellyfish mobility, as well as the musculature, it started to build a baby jellyfish. The first thing was to make a basic “mould” that looked like a jellyfish out of an elastic silicon polymer. This is the same stuff used in breast implant surgery because it doesn’t react with living tissue.

Protein nutrients were laid down on the silicon to map the network they wanted. Then they coated the silicon with rat heart tissue culture. The heart cells were encouraged by the protein coating to grow in exactly the same way as on an immature jellyfish.

After a few experiments, they succeeded in making the medusoid. This was then released into a salt-water tank. When a current was run through the water, the muscles tensed and contracted, curling the medusoid’s legs in and arching the dome. The elastic silicon “skeleton” allowed the legs to relax again when the current was shut off. This cycle of contraction-relaxation pumped water and pushed the organisms through the water like real jellyfish.

The team was determined to get things exactly right. The medusoid responds to the same electrical current by pumping water and moving at the same rates as its biological “ancestor”. It even creates the same vortices jellyfish do, in order to feed. It can’t change direction, though, unlike a jellyfish. Nor can it eat and it doesn’t have poisonous tendrils.

The medusoid can, therefore, be classified as an artificial pump built out of heart muscle. It mimics a biological pump made of heart muscle. It can be used for drug assay testing. The advantage is that the effect of a new drug on the pumping action will be directly observed. Thus, it could be of enormous use and it is being patented initially as a drug-assay tool. The team intends to re-engineer other, more complex marine creatures including octopi using the same techniques.

Once the technology stabilises, it should be possible to use human stem cells to make similar artificial biological devices. Eventually, it may be possible to take tissue from a human with, say, a damaged heart and repair that organ using these methods. It could take years of testing before that stage is reached. Many legal hurdles would also need to be crossed. But this is a stunning application of a combination of physics, engineering and biology.