'Heavy' mouse helps out tissue engineers


heavy_mouse

The 'heavy' mouse was created by feeding it a diet rich in carbon-13 and nitrogen-15 © Shutterstock

UK researchers have developed a tissue molecular mapping method that could help make lab-grown tissue much more like the real thing. The work could eventually cut the rejection of artificially grown tissues, such as heart valves.

Lab-grown tissues are often rejected by people’s immune systems when they are transplanted, so scientists suspected there must be unknown molecular differences between these tissues and natural ones. But until now there had been no way to compare the molecular structures of lab-grown and normal tissue to confirm this.

The problem was that although it's possible to image one-dimensional molecular structures of tissues using nuclear magnetic resonance (NMR) spectroscopy, which picks up signals produced by certain isotopes in proteins and cells, it was not possible to do this in a whole, live animal. This is because the heavy isotopes required for a detailed examination of a tissue are not naturally abundant and artificial enrichment was thought to disrupt biochemical processes.

Now, Melinda Duer and colleagues at the University of Cambridge, UK, have successfully enriched a mouse with heavy isotopes of carbon and nitrogen for the first time to compare its bone tissue with a lab-grown equivalent. They did this by feeding the mouse for 3 weeks with food enriched with the heavy isotopes and then used NMR to image the atomic structure of proteins in the mouse's bone tissue. ‘Heavy’ lab-grown bone tissue was created in a similar way to compare it with the mouse’s bones and tissues.

'I was blown away by the quality of NMR spectra we could obtain on real tissues,’ says Duer. ‘We quickly found that the general feeling that lab-grown tissues do not have the same atomic structure as native tissues was absolutely right. So then we used our NMR toolkit to understand the differences in terms of protein structure and composition and then devised a strategy to refine the way we grow the bone tissue in the lab so as to get to a more native-like tissue.'

Comparing how sugars bind with collagen in the space outside of mouse bone tissue cells revealed an unusual molecule. To their surprise, the team discovered it was poly(ADP ribose) (PAR), which was previously thought to only exist inside a cell as part of a DNA repair mechanism. This means PAR might provide the initial scaffold for bone mineralisation to occur – a discovery that could re-write textbooks.  

'This is truly innovative work, enabling new insight into tissue growth and opens up a whole range of new applications for the study of living organisms and the development of better laboratory or in vitro synthesis,’ says Sharon Ashbrook, an NMR expert at the University of St Andrews, UK. 'It might ultimately be possible to improve tissue engineering for replacement therapies in humans.’


Related Content

Chemistry World podcast - July 2014

2 July 2014 Podcast | Monthly

news image

We speak to artist Briony Marshall and art detective Warren Warren about the more artistic sides of chemistry

Living colour

8 April 2016 Premium contentFeature

news image

Fluorescent proteins can illuminate cells’ inner workings, but making them takes effort – and luck, as Andy Extance disco...

Most Commented

Ethanol to butanol conversion shows sustainable potential

13 January 2016 Research

news image

Borrowed hydrogen chemistry drives reaction to obtain useful fuel from biomass

Israeli chemists urge government to ban chemical weapons

21 July 2016 News and Analysis

news image

Open letter presses prime minister to ‘remove the curse of chemical weapons from the face of the Earth’