Jellyfish and the Therapeutic Potential of Collagen

The warm weather joined us on a trip to rocky Fleswick Bay in Cumbria back in July. As we finished our sandwiches, we saw the receding tide had exposed a patch of sand with waist-high water that was begging to be swum in.

I’d been splashing about with the children for maybe 10 minutes when my son saw a pale shape in the water, and without thinking he put his hand down to touch it.

I’m still unclear as to whether he did touch it, but at some point between putting his hand into the water and reaching down, he realised the patch of light was a jellyfish.

Now, part of my job as a parent is to not raise concern, so I quietly shuffled the three of us off to play in rock pools that had been satisfyingly warmed by the sun. I wondered whether all jellyfish sting, or just some of them - and whether there are some you need to watch out for more than others.

The Cumbria Wildlife Trust website was my first port of call. Here, I discovered that some jellyfish in UK waters do sting, but the Moon jelly (Aurelia aurita) we saw that day isn’t a problem for humans. I ventured further, and what was noticeable was how little is known about jellyfish venom, certainly not to the extent that substances derived from it are being tested in clinical trials.

The Moon jelly (Aurelia aurita) is not a stinging species.

Every year, the Marine Conservation Society in the UK publishes a report, and from this report it is clear that jellyfish numbers are increasing. Species of jellyfish not normally seen here are being spotted, including Crystal jellyfish (Aequorea victoria), of green fluorescent protein (GFP) fame. Crystal jellies usually live in warmer waters, a sure sign that sea temperatures are rising.

What’s more, the size of jellyfish gangs - actually known as jellyfish blooms - are getting bigger, with one of the causes being the removal of their natural predators, fish and turtles, by humans overfishing. Some species of jellyfish are eaten as a delicacy in east and southeastern Asian countries, and this demand is encouraging the establishment of fisheries around the world to harvest natural jellyfish blooms - one way to tackle rising numbers is to eat them. But not all fisheries are set up to supply the Asian food market.

Jellyfish are mostly water, held up by a substance called collagen. Collagen is the stuff of connective tissue - it’s strong and is the scaffolding that positions cells and tissues in the right places in animal bodies.

In the lab, we use collagen to coat the inside of culture vessels - it covers up the plastic to create a surface more friendly for cells to attach to and grow on. The collagen used comes from animals, and there is an obvious need to find alternatives. After spending much of the three years of my PhD growing heart and kidney cells on collagen, my supervisor decided it was time for me to learn how to extract collagen from its source. She sent me to the animal house for three adult rat tails and I spent the whole of the rest of the afternoon scraping the collagen from the tails into a Petri dish.

One company, Jellagen, is harvesting abundant Barrel jellyfish (Rhizostoma pulmo) from blooms at its fishery in south Wales not for food, but instead to respond to the need for collagen in medical applications. This collagen is still from animals, but the jellyfish are culled to control the size of population for conservation purposes. Harvesting the collagen for medical applications is a way to reuse animal material that would otherwise be thrown away.

Jellyfish collagen can be manufactured into different shapes and surfaces, and can enable the building of 3D complex cell models in the lab. Multiple cell types can be combined to create mini organs and tissues. And the more similar these models are to the inside of the human body, the more useful they can be for the testing of new medicines, the less reliant we need to be on testing medicines on animals.

Over the last 10 years or so, one focus of my research activities has been to make heart and kidney models of fibrosis. This has meant growing heart or kidney cells in the lab and injuring them with chemicals to simulate disease. Cells tend to react to this by sending out their own “help me!” chemicals, and by laying down collagen to form scars. I am used to thinking about collagen as the response to disease - and so the next part I found surprised me.

Ancient and modern Chinese medical books cite all manner of medicinal uses for eating jellyfish, including the ability to cure arthritis, treat high blood pressure, asthma, burns, ulcers… the list is long and not all proven with scientific rigor.

When collagen is broken down, as in cooking, a type of molecule called a hydrolysate is formed. And these collagen hydrolysates are clearly much more active than the native, structural form of collagen. It turns out that collagen hydrolysates can relieve the joint pain associated with arthritis and enhance skin health in clinical trials. They can increase mobility and make structural improvements to joints. Collagen hydrolysates from Flame jellyfish (Rhopilema esculentum) can heal wounds and prevent massive blood loss. Wound dressings made from collagen speed up wound healing.

What is more, some studies have indicated that the collagen hydrolysates from Flame jellyfish could also contain ACE inhibitor molecules - molecules that stop the activity of Angiotensin-converting enzyme (ACE). This is the protein that converts Angiotensin I to Angiotensin II, which in turn constricts blood vessels to increase blood pressure. You might remember we met the first ACE inhibitor to be approved for the treatment of high blood pressure when talking about pit vipers.

You’d not believe it, but ACE inhibitors have been found not only in pit viper venom and Flame jellyfish hydrolysates, but they have also be found in hydrolysates from plants, chickens, milk, and other marine animals. Such is my interest in the regulation in blood pressure that I’m going to come back to this bombshell in a later post!

The Barrel jellyfish (Rhizostoma pulmo) is fished off the coast of south Wales for its collagen.

Further Reading

Faruqui, N., Williams, D. S., Briones, A., Kepiro, I. E., Ravi, J., Kwan, T. O. C., Mearns-Spragg, A., Ryadnov, M. G. (2023) Extracellular matrix type 0: From ancient collagen lineage to a versatile product pipeline – JellaGel™ Materials Today Bio, 22:100786.

Larder, C. E., Iskandar, M. M., Kubow, S. (2023) Collagen Hydrolysates: A Source of Bioactive Peptides Derived from Food Sources for the Treatment of Osteoarthritis Medicines, 10(9):50.