NYU Abu Dhabi study brings hope of ‘regrowing’ damaged organs

From mice to octopuses, many species are better are regeneration than we mammals - so what can we learn from them?

The liver is so remarkable among the body’s organs that even the Ancient Greeks wrote about it.

They incorporated it into the story of Prometheus, who – chained to a rock as punishment for stealing fire and giving it to humanity – had part of his liver eaten each day by an eagle, only for it to regrow by night.

While this mythological tale exaggerates the liver’s ability to repair itself, even in the real world the organ’s powers of regeneration are striking.[Regrowing organs] would be something transformative for a lot of people who suffer from heart attacks where part of the heart muscle dies, or people who have damage to their kidneysProf Kirsten Sadler Edepli

If two thirds of the liver of a mouse is removed, for example, the organ will regrow to its full size in less than a week.

Research work at NYUAD is now trying to unlock the secrets of organ regeneration in the hope that it could help people with damaged hearts or kidneys.

While regeneration in mammals is restricted largely to the liver, many creatures can regrow other parts of their body. Salamanders, for example, can regrow limbs, while zebra fish can repair spinal cords, grow new fins and even regenerate their heart.

“Most animals can regenerate pretty much everything. We mammals are the outliers,” said Kirsten Sadler Edepli, a professor at the university.

Prof Sadler Edepli and her co-researchers are interested in the chemical “decorations” on the genome (the complete set of an organism’s genes) that are involved in organ regeneration.

Prof Kirsten Sadler Edepli is part of the research team at NYUAD. ‘Most animals can regenerate pretty much everything. We mammals are the outliers,’ she says. Courtesy NYUAD

These chemical decorations, known as epigenetic modifications or, collectively, as the epigenome, are distinct from the genetic instructions coded in each organism’s DNA.

In a newly published study led by Dr Chi Zhang, a research scientist in Prof Sadler Edepli’s team, mice were analysed to take a closer look at the epigenetic signals involved in liver regeneration.

Samples of normal mouse liver cells were examined for their epigenetic code, as were regenerating livers taken from mice where the organ was growing back after part of it had been removed.

The researchers found that, in normal liver cells, genes that promote regeneration of the liver had a particular epigenetic modification called H3K27me3.

When the liver is regrowing, this chemical label – likened by Prof Sadler Edepli to a brake pedal – is removed, enabling these important genes to drive cells to divide so they can multiply and the liver can regrow.

The study – thought to be the first to detail the epigenetic patterns involved in liver regeneration – was published in the journal Nature Communications as, ‘Chromatin states shaped by an epigenetic code confer regenerative potential to the mouse liver’.

Dr Chi Zhang, a research scientist in the NYUAD team that studied how mice regenerated their livers. Courtesy NYUAD

Taking more than three years, the research was a team exercise, with the computer-based analysis carried out by Dr Zhang and other scientists in Prof Sadler Edepli’s lab doing the experimental work.

If researchers can understand this field better, it may be possible to help damaged organs regrow. “That would be something that would be transformative for a lot of people who suffer from heart attacks where part of the heart muscle dies, or people who have damage to their kidneys,” Prof Sadler Edepli said.

Prof Sadler Edepli is now at the Marine Biological Laboratory in Cape Cod, US, studying an animal with a remarkable ability to regenerate limbs – the octopus.

She is collecting material to be analysed back in her Abu Dhabi lab. “They regenerate like crazy – they can have multiple arms regenerating,” she says. “I’m here to try to collect samples from the regenerating arms to determine if they have the same gene expression profile as the mouse liver and if it is dictated by the same code.

“It’s a long shot but that’s why I think biology is fun – you come up with an idea and test it. A lot of the time we don’t get it right but when we do it is exhilarating.”