May 2014
Marc Turner Screen Capture

There will be (stem cell derived) blood

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Over the next three years, a team of Scottish scientists hope to prove that the blood they are making from stem cells is as good as — or even better — for transfusions than the ordinary donated kind.…

Over the next three years, a team of Scottish scientists hope to prove that the blood they are making from stem cells is as good as — or even better — for transfusions than the ordinary donated kind.

Although it has hardly raised an eyebrow in Canada, this potentially game-changing research has been big news in the United Kingdom where it was featured in the Daily Mail, a splashy tabloid with a circulation of 1.75 million. As the Mail suggested, this “could lead to a future where artificial blood is used more regularly than donated blood.”

Prof. Marc Turner, pictured left, leads a lab at the University of Edinburgh that has successfully produced red blood cells from human embryonic stem cells and induced pluripotent stem cells (stem cells drawn from the skin that are reprogrammed to an embryonic-like state).  The researchers have made a careful study of the cells’ properties in test tubes and Petri dishes. “But the only real way of finding out if these are the Real McCoys and that they fit in the circulation the same way as normal red blood cells is do a proof of principle, ‘first in man’ study,”  says Prof. Turner, the Medical Director at Scottish National Blood Transfusion Service  and leader of the  £5 million ($9.27 million) project.

How could this stem cell derived blood be better? The human body produces millions red blood cells every minute of every hour. These cells, which transport oxygen around the body via their hemoglobin content, last about 120 days.  So when you donate blood at your local clinic, some of it might be 119 days old and ready for the scrap heap. Stem cell generated red blood cells, however, are all brand, spanking new.  Ideally, then, they should all put in a good four months’ work in the bloodstream after transfusion. That’s what Prof. Turner’s team wants to find out.

The Scots aren’t the first to do this. In a 2011 paper published in BloodFrance’s Dr. Luc Douay showed that red blood cells derived from adult stem cells performed “favorably” compared to “native red blood cells” when transfused into a test subject.  As well, labs around the world have been successful in producing red blood cells using embryonic stem cells and induced pluripotent stem cells.

The problem has been “scaling up” the number of red blood cells required to do clinical trials. Dr. Douay used hematopoietic (blood-based) stem cells for his breakthrough.  “But researchers don’t have culture conditions that can support a very large expansion of hematopoietic stem cells,” says Dr. Julie Audet, Associate Professor of Biomedical Engineering at the University of Toronto.  “So this step of amplification of the starting material is causing problems.”

Another challenge, says Dr. Audet, is that red blood cells derived from embryonic or induced pluripotent stem cells lack maturity: the hemoglobin they carry is more like the stuff of newborns than that of adults.

While Prof. Turner acknowledges the fetal quality hemoglobin isn’t ideal, it is functional. “It will do for the time being. We have some ideas about how we might try and nudge the cells to an added degree of maturity.  It’s important, but it’s not a showstopper at this stage.”

As for the “scaling up” challenge, he thinks they have that figured out — at least for their current very small (three-patient) study. “It will only require relatively modest volumes of red cells. After that, on the big assumption that that we will be successful, we will be looking to go into proper clinical study. That’s when we will start to confront the issues of scale up.”

So what does it all mean? Are blood donor clinics destined to go become a relic of a bygone era?

Not any time soon, says Prof. Turner.

“This is years or decades away. We don’t want people to stop donating blood just now, please.”

The more immediate application, he says, could be using the process for people with thalassemia, a genetic disorder that causes destruction of red blood cells.

“These patients are dependent on long-term red blood cell transfusions. They survive well now compared to decades ago, but they do have a problem with iron loading. One of the potential advantages of having a younger cohort of red cells is they should last longer in circulation. That would offer a clinical advantage.”

So the potential short-term impact is important, but limited. Longer term, however, this could change everything.

“In the very long term, it may be possible to generate red cells for general use,” says Prof. Turner.

“That obviously would have an advantage in those countries that don’t have a secure supply of blood. Developed countries like Canada and the UK have sufficient sources of cells and pretty secure and safe blood supplies. But we shouldn’t take that for granted.  Certainly, we’re all familiar with problems with (transfusion transmitted) infections in the past, like Hepatitis C. And we’ve had problems with Creutzfeldt–Jakob disease here in the UK.”

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