SCOTTISH scientists have been given the go-ahead for the world’s first trials in humans of synthetic blood, The Scotsman can reveal.
Researchers based at the Scottish Centre for Regenerative Medicine (SCRM) in Edinburgh hope to use stem cells to manufacture blood on an industrial scale to help end shortages and prevent infections being passed on in donations.
The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has now granted a licence so scientists can make blood from stem cells which can be tested in humans – the first step towards large-scale clinical trials, which will hopefully lead to the routine use of blood created in this way.
The researchers also revealed they will now turn their attention to using stem cells – early cells capable of turning into different types of tissue – from adult donors as opposed to the more controversial embryonic ones which have so far formed the basis of their work.
As well as the blood research, the licences will also allow scientists in the coming years to create stem-cell products to treat patients who have suffered a stroke and people with Parkinson’s disease, diabetes and cancer. But much of the attention has focused on how stem cells could be harnessed to create blood products – seen by many as the “holy grail” of blood research.
While other researchers have been granted licences to develop stem-cell products for human testing, the Scottish team is the first in the world to use the permission to trial synthetic blood.
The granting of the licence allows work to begin at the SCRM’s new GMP (good manufacturing practice) Cellular Therapy Manufacturing Facility.
The news was announced by Edinburgh University, the Scottish National Blood Transfusion Service (SNBTS) and the company Roslin Cells.
The facility is jointly operated by SNBTS and Roslin Cells and will now be allowed to manufacture “advanced therapy medicinal products” for use in clinical trials. An additional “specials” licence has also been awarded to allow them to create therapies for use in specific patients. It has taken 18 months of work to get the licences awarded.
Project leader Marc Turner, director of SNBTS, said getting the licences was “absolutely crucial” to advancing their work.
“This is a very high specification facility that we have built in Scotland for manufacturing cells therapeutics. And because this is a blood project we need the highest possible standards of cell culture and manufacture,” he told The Scotsman.
“We wouldn’t be able to do that project in any of the other facilities we have available.”
News that Scottish scientists were leading the quest to turn stem cells into usable blood first emerged in 2009. Then in 2010 the researchers revealed that they had managed to turn stem cells from spare IVF embryos into red blood cells.
Since then they have continued their work in a bid to create blood of the universal O-negative blood type which can be given to most people without fear of rejection.
Prof Turner said a key difference in their work going forward would be the use of stem cells derived from adult tissue – known as induced pluripotent stem cells.
The cells are taken from an adult and specially treated so they regress to a state with qualities similar to embryonic stem cells, which are believed to hold the most promise of being able to transform into different types of cell and tissue.
Prof Turner said: “In the first part of the project we used human embryonic stem cell lines and one of the problems with using those lines is you can’t choose what the blood group is going to be.
“Over the last few years there has been a lot of work on induced pluripotent stem cells and with those an adult can donate a small piece of skin or a blood sample and the technology allows for stem-cell lines to be derived from that sample.
“This makes our life a lot easier in some ways because that means we can identify a person with the specific blood type we want and get them to donate a sample from which we could manufacture the cell lines.”
A move away from embryonic stem cells would also help appease concerns of pro-life campaigners who have condemned the use of embryos as a way of harvesting “spare parts” for medical research.
Prof Turner said they were making “good progress” with their project and hoped trials in patients could start in the near future. He said: “We hope that in the next two to three years we will be putting together all the kind of manufacturing capability and also the regulatory and quality requirements to start clinical studies.”
Early trials would involve injecting patients with small amounts of the blood before moving on to larger transfusions in a bigger group of people.
Janet Downie, Roslin Cells’ chief operating officer, said receiving the licences from the MHRA to continue their work was an “important milestone”.
“Within Scotland we now have a key asset and also a talented multi-disciplinary team capable of delivering cell therapies for patients and developing the cell therapy economy in Scotland,” she said.
Health secretary Alex Neil said: “Scotland has a world-class reputation in regenerative medicine and stem-cell research. The completion of this state-of-the-art facility will further advance our understanding of the debilitating diseases this field seeks to address.”
Stem-cell blood needs to cost less than £500 a pint
If scientists succeed in producing blood from stem cells it could help overcome the recurring problem of shortages from donations, which often lead to appeals for donors of certain blood groups to come forward.
Producing blood products on an industrial scale could help provide supplies for use in hospitals, as well as in war zones and at the scene of accidents.
It would also combat the risk of new infections being transmitted between donors and recipients – a major concern as new diseases emerge before tests can be developed to identify them in blood supplies. The decision by the Scottish researchers to move away from using embryonic stem cells to adult stem cells is also a significant step.
It will allow them to more easily choose the blood type they desire to create – in this case the universal O-negative group – as well as avoid criticism from those still concerned about the use of embryos in stem-cell research.
Once the first small-scale trials of the stem-cell blood have been completed, researchers hope to move on to bigger trials. But this holds its own challenges as they will need to develop a way of scaling up production to produce the quantities of blood required.
To produce enough blood to supply the health system, industrial “bio-reactors” will be required.
Another challenge will be to keep costs down so the stem-cell blood products are no more expensive than blood collected through donations. Making a pint of blood ready for transfusion costs around £180, but the extra costs linked to testing and collection bring the price to about £500 a pint.
Analysis by Marc Turner: With an ageing population and rise in chronic diseases, the demand for blood will increase
SCOTLAND as a nation has kept abreast of the demand for blood over the last ten years, partly by changing the services we provide to donors.
Our donor base is changing as society changes, and we are communicating with them in new ways such as text and e-mail to make donations more suitable for people with busy lives.
We are facing an ageing population and a likely increase in the amount of chronic and degenerative disease over the coming decades.
That is likely to increase demand for blood at a time when there will be fewer, younger donors around. There is no doubt that it is a longer term concern.
If or when the project comes to fruition, it may help us to augment the regular blood supply, particularly in times of shortage when people are on holiday, or when there is a sudden increase in demand. But this is a long-term project, and we do not want people to stop donating blood. We are 100 per cent dependent on our blood donors and their generosity, and that is not going to change any time soon.
There is most pressure on the O RhD negative group, or so-called universal donor blood. It is a type that is compatible with the vast majority of people, and which we use in emergency situations like accident and emergency departments and maternity units and that is where we would hope to support emergency stocks.
Thereafter, there are smaller populations of people who are difficult to transfuse, and it may be that in due course we can use this kind of technology to support them specifically as well.
But while this project is about Scotland and the sufficiency, quality, and safety of our blood supply in the long term, it is also about global insufficiencies and risks. Worldwide, blood supply is heavily skewed towards ourselves and other developed countries. There are just over 100 million units of blood given around the world each year, but around 60 per cent of those go to those of us lucky enough to live in developed nations, and very large parts of the world such as sub-Saharan Africa have very poor blood supplies. Another key issue is transfusion-transmitted infections. We have had serious problems in the past in this country with infections like HIV, Hepatitis B, and Hepatitis C, although the testing regimes we now have in place means the blood supply is now very secure.
But there are always new, emergent infections on a worldwide basis. Whereas once we would have considered them another country’s problem, international travel and trade means they can impact on us.
We have been very fortunate in getting the support of the Wellcome Trust and the Scottish Funding Council, because this is not a normal research project which is going to deliver in two or three years’ time, this is something which will take many years to develop.
• Professor Marc Turner is medical director for the Scottish National Blood Transfusion Service.