Sea Cucumbers: The Key to Organ Regeneration

Picture this: on your morning walk, a speeding car suddenly rams into you. Among other injuries, your liver is annihilated. You are rushed to the hospital, only for the doctors to say the damage is irreversible. That leaves one last option: replacing the organ entirely. The doctor breaks some more bad news: there’s no available donors in your area. Normally, your odds wouldn’t be good. But with new research being done on regenerative medicine, maybe one day you could just grow a new liver.

As of now, humans can naturally repair or regenerate a number of tissues, like when healing a cut, but nothing close to full organs. Normally, if we lose an organ due to damage or disease, we’d have to get a transplant. Since there’s been an increasing shortage of organ donors, scientists are looking deeper into the unique regeneration abilities of certain animals to see if these traits can be applied to mammals.

Tons of animals, especially invertebrates living in the ocean, have regenerative abilities. You’ve probably heard that if a starfish loses a limb, it’ll grow back. Sea cucumbers, which are related to starfish, are special because they can do this with their entire digestive system!

When we see a scary animal, we might run away or try to fight back. Sea cucumbers, on the other hand, defend themselves by literally shooting their inner organs out of their mouth or anus in a process called evisceration. The coolest part: the organs grow back within a few weeks or months!

While humans and sea cucumbers might seem totally different, they’re actually very similar evolutionarily. In fact, sea cucumbers are the closest non-chordate relatives of humans. Non-chordates are animals without a notochord, a flexible, rod-like structure that supports the body.

According to evolutionary biologist Dr. Joseph Ryan at the University of Florida, both humans and sea cucumbers are part of a larger group of animals called deuterostomes. However, one species has a huge capacity for regeneration, and the other has, well, close to none. Mapping out the sea cucumber genome to compare it to the human genome therefore, could be the key to understanding human organ and tissue regrowth.

In collaboration with Dr. José García-Arrarás’ research group at the University of Puerto Rico, Dr. Ryan and his team set out to do just that. Together, they sequenced, assembled, and annotated the genome of the sea cucumber, focusing especially on the melanotransferrin gene family, which was suspected to play a crucial role in regeneration.

The significance of melanotransferrin was first realized by biologist and sea cucumber expert Dr. García-Arrarás through a process called RNA sequencing. In other words, the scientists created a profile of the level of expression of every gene in the genome before and after evisceration.

The García-Arrarás group found that the expression of melanotransferrin, which started off relatively low, shot up after evisceration, suggesting that it could be involved in regeneration. But without the full genome, it was difficult to interpret these results. The sequencing of the genome illuminated the fact that sea cucumbers have four copies of melanotransferrin, which is odd since humans and other animals only have one copy. While the application of this discovery to humans might not seem clear, Dr. Ryan believes that big discoveries are only possible with a strong knowledge base.

So we know some of the genes involved, but how does the process of regeneration actually work? Science journalist Dr. Stephanie DeMarco says it’s all about dedifferentiation. For a cell to look and behave a certain way, it has to express certain genes. When regenerating, cells first change the expression of many genes so that they revert to being stem cells (cells that can turn into any cell in the body). From there, they can alter the gene expression to become any type of cell (like a muscle cell or neuron), a process known as redifferentiation.

Dedifferentiation happens rarely in humans, but scientists are studying how it works in animals to one day apply what they learn to human disease. Humans can regenerate tissues to some extent, especially when healing wounds, but obviously we can’t regrow an arm. Many researchers studying regeneration are trying to figure out why we can only regenerate some aspects of our biology.

So how long before we can grow back that liver? Dr. Ryan gives it a 25 year timeline. Right now, tons of people are doing stem cell research, but the work on echinoderms is still in its early stages. The next step would be to apply what’s known in invertebrate regeneration to models that are more similar to humans. This would allow us to figure out how to make a human gene function the same as its sea cucumber counterpart.

The work Dr. Ryan and others are doing on esoteric animals like sea cucumbers may or may not provide applicable solutions, but if a million scientists look in uncommon places, eventually someone’s going to find something with a major impact. In the words of Dr. DeMarco, “Don’t discount the weird animals.”