10 years of the MRC Centre for Regenerative Medicine

The MRC Centre for Regenerative Medicine was established in 2008, Directed by Professor Sir Ian Wilmut. CRM has had 10 incredible years with many, many highlights. As part of our 10th anniversary celebrations we wanted to share some of those highlights with you: 10 stories to be precise.

2009 - Safer stem cells for humans

Dr Keisuke Kaji made a major breakthrough in 2009. He was working on refining the technique of making induced pluripotent stem (iPS) cells. The IPs technique involved reprogramming adult stem cells to behave like embryonic stem cells by adding four Yamanaka factors Oct4, Sox2, Klf4, and cMyc to the adult stem cells using viruses. Keisuke wanted to develop a safer technique by avoiding the use of viruses. Instead of using a virus, he successfully refined the technology by introducing the four factors using a pasmid (a circular piece of DNA found in bacteria). His work was published in Nature in March 2009 and has since been cited more than 1400 times.

Keisuke Kaji is now a Professor of Biology of Reprogramming and holder of a prestigious MRC non-clinical fellowship. Keisuke recently published a new technique to improve the efficiency speed of the conversion of one cell type to another (cell reprogramming). 

2010 – Professor Sir Ian Wilmut passes on the baton to Prof Charles ffrench-Constant

The initiative to establish CRM, a new centre focussed on stem cells and regenerative medicine, was the brainchild of CRM’s first Director Professor Sir Ian Wilmut. After Ian’s ground-breaking work to establish CRM, it was Prof Charles ffrench-Constant who took the helm in 2010 to become CRM’s second director. It was also the year that Charles and Prof Siddharthan Chandran played a pivotal role in receiving a £10M donation from the Harry Potter author JK Rowling for the University to set up the Anne Rowling Regenerative Neurology Clinic. The Clinic draws on CRM and the University’s world-class strength in neuroscience, stem cell research and regeneration.

The Anne Rowling Regenerative Neurology Clinic was officially opened in 2013 and to this date CRM remains closely linked to the Anne Rowling Clinic.

2011 – MRC CRM staff and students move into the Centre for Regenerative Medicine building

It took 5 years of planning and 3 years to build, but in 2011 the first CRM staff moved into their new home at 5 Little France Drive. The £56 million purpose-built facility provides home for up to 250 scientists and contains state-of-the-art laboratory space and a clinical translation unit - enabling the production of cells at GMP-grade (Good Manufacturing Practice), suitable for future therapeutic applications. In May 2012 CRM organised a symposium to honour Prof Sir Ian Wilmut and mark the official opening of the new building. The event drew more than 350 attendees from across the globe.

Since the move CRM has grown in numbers and the building has more than exceeded its maximum capacity. Fortunately, new funds have been secured to build a new £55 million research facility adjacent to the CRM building, which will house some of the CRM researchers and clinicians.

2012 - Better understanding of how stem cells are controlled

Prof Ian Chambers’ group made fresh discoveries regarding the gene regulator Nanog. Named after Tír na nÓg, the mythical Celtic land of the ever-young, Nanog controls the efficiency with which stem cells create duplicate cells. High levels of Nanog make stem cells continue to duplicate. Low levels increase the chance stem cells will become another cell type. Nicola Festuccia, a former PhD student in the Chambers group, found that a specific gene regulator, Essrb, was most strongly switched on by Nanog. When Esrrb was stopped from being switched on, Nanog was no longer able to tell the stem cells to duplicate. The findings, published in Cell Stem Cell, give scientists greater control over stem cell behaviour for use in medicine.

Nicola, one of 162 PhD students CRM has trained over the last 10 years, has since moved on to do a Postdoc at the Institut Pasteur in France and has just started as a Principal Investigator at the Institute for Clinical Sciences in London. At an event to mark CRM at 10, Nicola received a special recognition award for his success. 

2013 - Bacteria’s hidden skill could pave way for stem cell treatments

Prof Anura Rambukkana and his team at CRM found that bacteria were able to change the make-up of supporting cells within the nerve system, called Schwann cells, so that they took on the properties of stem cells. Because stem cells can develop into any of the different cell types in the body – including liver and brain cells – mimicking this process could aid research into a range of degenerative conditions. They were studying the bacteria that cause leprosy, an infectious neurodegenerative disease. The study found that in the early stages of infection, the bacteria were able to protect themselves from the body’s immune system by hiding in the Schwann cells. Once the infection was fully established, the bacteria were able to convert the Schwann cells to become like stem cells. 

The research was published in the journal Cell and made headlines in major news portals around the world and in all top ranking journals including its selection to Best of Cell 2013 collection from Cell Press.

2014 - Cell therapy trial offers new hope to liver disease patients

Professor Stuart Forbes and his team received £2 million funding from the Medical Research Council and Innovate UK to start a clinical trial for liver disease patients using a new cell therapy to treat the condition. It was the world’s first clinical trial of a new type of cell therapy to treat liver cirrhosis. To date, the only successful treatment for end-stage liver cirrhosis is liver transplant. The new therapy is based on a type of white blood cell called a macrophage, which is key to normal repair processes in the liver. Scientists take cells from the blood of patients with liver cirrhosis and turn them into macrophages in the lab using chemical signals. These new cells are re-injected into patients in the hope they reduce scarring and help to rebuild the damaged organ from within. The Scottish National Blood Transfusion Service collaborated on the development of the cell manufacture process in the GMP Cell Therapy facility, housed in the CRM building. Update: The results of the phase 1 clinical trial have just been published in Nature Medicine. The study showed that the macrophage cell therapy is safe. node/3231

2015 - Skin scent offers Parkinson’s hope

In 2015, Dr Tilo Kunath started a research project to investigate whether Parkinson’s disease could be diagnosed from skin swabs. The research was prompted by a woman, Joy Milne, who has an acute sense of smell. She approached Tilo at one of his public engagement events at CRM, organised specifically for people interested in Parkinson's research. At the event she mentioned she had noticed that people with Parkinson’s emit a unique, subtle odour. Researchers believed the scent may be caused by a chemical change in skin oil known as sebum that is triggered by the disease. Joy Milne’s question led to a small pilot study with Prof Perdita Barran's group from Manchester University where Joy correctly identified which people from a group of 24 had Parkinson’s. She did so by smelling T-shirts that they had worn for a day. They hoped to identify the molecules responsible for this, to then develop ways to detect patients in the early stages of Parkinson’s and follow the progression of the condition.

The story has since been widely covered in the media, including a 30-minute BBC documentary in January 2018. Dr Tilo Kunath has received additional funding from Parkinson’s UK to co-lead the development of a new technique that could improve the effectiveness of cell therapies for Parkinson’s patients.

2016 - Notch3 drives Cholangiocarcinoma

Scientists at the CRM identified a molecule that drives the development of bile duct cancer. The research in mice and human cells sheds new light on what triggers the disease and how the illness progresses. The research team say that further research will be needed but the findings could eventually reveal opportunities to improve diagnosis and develop new therapies. They focused on a family of molecules called Notch, which are critical for the formation of bile ducts as the liver develops in an embryo.

Miss Rachel Guest and CRM Director Prof Stuart Forbes, looked at whether these molecules are involved in bile duct cancer.

2017 - Brain cancer screening hope

Dr Steve Pollard and his team have used CRISPR/Cas technology to modify the genes of neuronal stem cells in different ways, including engineering two mutations found in glioblastoma (deletion of the tumour suppressor gene TP53 and a point mutation H3F3A). This will allow the more detailed study of the precise effects of different genes and mutations in neuronal stem cells, providing models for glioblastoma to investigate the disease. The paper is published in the journal Development (2017 ; 144: 635-648; doi: 10.1242/dev.140855) and featured in the Cancer Research UK’s blog http://scienceblog.cancerresearchuk.org

2018 - Stem cell liver implants show promise

New research suggests liver tissue grown from stem cells could one day replace the need for liver transplants. A study by Professor David Hay and colleagues found liver tissue implants supported liver function in mice with a type of liver disease. The team say the advance offers early-stage progress towards developing liver tissue implants for people. The implants were produced by turning stem cells into cells with characteristics of liver cells in the lab. The cells grew into tiny balls in a dish for up to a year, but did not adopt the 3D structure of liver tissue. This is just one of the more than 500 papers published from the Centre over its first 10 years. This success has helped to attract £126 in funding over that time period.

2008 – 2018 EuroStemCell: going from strength to strength

EuroStemCell.org aims to help people across Europe make sense of stem cells by providing curated and accurate information. The site is part of an EU funded project led from CRM by Prof Clare Blackburn and public engagement specialists. The EuroStemCell network, established in 2006, unites more than 33 partner institutions across Europe, representing 400 stem cell research groups. There is no other partnership of this size, maturity and depth in Europe. Eurostemcell.org has over 1 million unique visitors annually from 239 countries and consistently ranks in the top 5 of Google searches. The website is available in 6 languages and includes hundreds of educational resources, fact sheets, films, digested reads, interviews and articles.

Over the years many CRM students and researchers have contributed to the project by translating, writing and reviewing content, developing resources and delivering events. All these contributions have helped to turn the project into the success it is today.

The future

In October 2017 Stuart Forbes marked the start of construction of the Centre for Tissue Repair (CTR) with Castlebrae Community High School pupil Kelsey Wallace, our first summer intern from the school and therefore youngest member of staff. With CRM, the new CTR will form the Institute for Regeneration and Repair (IRR). Stuart said, 

This marks the start of a new chapter for Regenerative Medicine in Edinburgh, CRM has grown beyond initial expectations and the CTR builds on that success.

Stuart Forbes