Donated organs that would normally be discarded as being unsuitable for transplant could be used to generate new livers for transplant and to create human models to better understand liver diseases.
Professor Massimo Pinzani and Dr Giuseppe Mazza are pushing the boundaries with their research into building the human liver using a process called ‘decellularization’ where all of the cells from a donated organ are removed leaving only the 3D ‘scaffold’ between the cells intact.
The scaffold is then repopulated with donated replacement human liver cells and treated with growth factors to ‘recellularize’ and aid the growth of a new functional liver. The liver cells are isolated in the lab at the Royal Free Hospital or acquired from Promethera, a university spin-out company based in Brussels.
This is the first time research has been carried out into decellularization of the liver and is a break from the traditional approach of transplanting.
Dr Mazza and other members of the clinical and research team are on call round the clock to receive donated livers that cannot be used for transplantation due to abnormalities, with the most common reason being the build-up of fat within the liver cells. The Royal Free London is the first centre on the list in all of the UK to be offered livers that are unsuitable for transplantation and has received over 100 livers during the last three years.
Dr Mazza said: “There were approximately 900 livers not suitable for transplantation in 2014 and 1 in 10 of these came to the Royal Free London to help our research – for us a call in the middle of the night to say a liver is available no problem. We are most excited about taking the leap towards regenerating new livers and hope to raise awareness that being an organ donor can also save lives by contributing to ground breaking research, as well as helping those who need a transplant”.
Tissue Access for Patient Benefit based at the Royal Free London has helped to establish the collection of unsuitable organs by providing assistance with ethics; and interaction with the NHS Blood and Transplant Special Health Authority.
Professor Pinzani and Dr Mazza are in the early stages of their research and currently investigating the best order and time to repopulate the liver with replacement human liver cells. The researchers are at this time studying small ‘cubes’ of the liver scaffold.
Professor Pinzani said: “We believe everything done on a small scale can be done on a large scale and so are learning how best to repopulate the decellularized liver starting with cubic areas measuring just 5×5×5mm”.
After recellularization the new liver is matured in a chamber donated by Harvard Apparatus that can be controlled remotely using a smart phone app.
Professor Pinzani and Dr Mazza have recently been awarded £80,000 by the BRC to develop their research. Professor Pinzani said: “We would like to extend our thanks to the BRC for their support with our research which raises the prospect of growing livers that can be transplanted into patients”.
The Royal Free Charity has also donated £100,000 towards the research.
58-year-old Andy Frame from Camden has spent the last 30 years travelling all over the world working in pyrotechnics. However Andy is also on the waiting list for a liver transplant as a patient at the Royal Free London.
Andy, who was diagnosed with liver cancer in August 2011, said: “Luckily my cancer has not spread so I have been able to continue visiting amazing places around the world as part of my job. However, I have had three interventions to remove tumours, along with a liver resection and radiofrequency ablation treatment. Unfortunately chemotherapy isn’t an option for me as it risks tumours in the liver breaking up and spreading”.
at the London Palladium
Andy said of Professor Pinzani and Dr Mazza’s research into building the human liver: “This really is revolutionary and such an exciting prospect for anyone who may find themselves in my situation in the future. I have been on the transplant list for over two years but to imagine that one day patients may be able to have their own bespoke replacement livers built instead is excellent”.
The average waiting time for a liver transplant in the UK is 145 days for adults and transplants are specifically organised based on patients’ blood type, body size and medical condition. As Andy has had previous surgeries his wait time is longer than average due to added complexities of the transplant operation.
To read Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation, a scientific report published in Nature click here.
To find out more about joining the organ donor register visit www.organdonation.nhs.uk.
To find out more about the Tissue Access for Patient Benefit project click here.
