In 2009, a research team in Scotland embarked on the ambitious effort to make blood cells in a lab. Five years later, project director Marc Turner has announced that they’ve whipped up a batch that could conceivable be transfused into a patient.
If the University of Edinburgh researcher’s claim pans out, artificial blood, often the stuff of science fiction, may revolutionize how clinics administer life-saving treatments. The American Red Cross estimates that more than 41,000 blood donations are needed each day, with a person needing a transfusion every two seconds. A breakthrough that leads to wide-scale blood factories may ultimately mean an end to the kind of procedure-related infections and blood shortages common in developing regions.
Turner says human trials are slated to begin as early as 2016. “Producing a cellular therapy which is of the scale, quality and safety required for human clinical trials is a very significant challenge,” he said. “It will be an important step forward to enable populations all over the world to benefit from blood transfusions.”
Up until the last decade, the search for a viable form of man-made blood has centered mainly on developing blood substitutes, substances such as hemoglobin-based oxygen carriers, a kind of modified blood plasma derived from animal or expired human blood, and an entirely synthetic formulation based on perflourocarbons (PFCs). Without actual red blood cells, these solutions were designed as a way to simply deliver oxygen throughout the body. While potentially useful, especially during an emergency, previous experiments have revealed blood substitutes may also pose a host of life-threatening complications.
In the 90s, industry giant Baxter Healthcare Corporation was in the midst of testing a haemoglobin-based oxygen carriers substitute called HemAssist on human subjects when it became apparent that those patients died at a noticeably higher rate than those who received donated blood. Consequently, the study was quickly canceled. The Food and Drug Administration has yet to approve the sale or use of haemoglobin-based oxygen carriers substitutes (HBOCs).
“Synthetic or cross-linked hemoglobins (HBOCs) tend to be toxic probably because they bind nitric oxide and cause constriction in the microcirculation, while perflurocarbons (PFCs) have a short circulating half life and linear oxygen binding so they require repeated infusion and very high inspired oxygen to be effective,” Turner explained. “What we [and others] are doing is culturing red blood cells from stem cells, so these should have the same characteristics as those occurring naturally in your or my blood.”
Red blood cells are produced by a unique class of stem cells known as pluripotent hematopoietic cells. Taken from the Greek terms “haima,” (blood) and “poiesis” (to make), these “mother” blood cells are capable of forming every type of blood cell. In essence, they serve as the source code from which blood is then produced in the body.
Turner’s method, through the application of culturing techniques that foster the kind of conditions found in the body, takes a similar type of stem cell called induced pluripotent cells and nudges them to generate universally-compatible “O” negative blood, a rare blood type present in no more than 8 percent of the world’s population.
And whereas blood cells start to degrade shortly after they’re collected from a donor, the ability to manufacture them on-demand eliminates virtually any potential health concerns that may come from using units kept on the shelf for longer periods. While it’s not known whether older blood is actually harmful, medical experts have recently begun looking into the possibility, according to a report in the New York Times.
Turner’s group isn’t the only one attempting to safely and effectively replicate this naturally-occurring process. In 2010, scientists at the Pentagon announced that they’ve figured out a way to developed stem cell-derived blood for injured soldiers in the battlefield using discarded umbilical cords. Meanwhile, researchers at the Indian Institute of technology in Madras told the Times of India last year they’ve perfected a procedure that yields a quadrillion red blood for each 450 milliliter RBC bag, a much greater concentration compared to the 2 trillion red blood cells contained in a unit of donor blood. At the time it was reported, the group said that the technology will undergo human trials in three years.
For the UK-based team, nailing down a system that consistently produces more than enough red blood cells remains one of their biggest challenges. “The minimum cell count requirement for transfusion are enormous numbers and way beyond current capacity both in human cell therapies and other culture systems such as monoclonal antibody production,” Turner said. “To be reliable, we are working on not just scaling up the process but also increasing the density of the culture systems.”
Looking ahead, he says they hope to conduct the first human trials involving man-made blood with three volunteers. If successful, they’ll build upon the results in a follow-up study with patients suffering from beta thalassaemia, a blood disorder that hampers the body’s natural production of hemoglobin.
“We are at least a decade away from any routine clinical application at the moment,” he added.