RED blood cells generated in a lab have been successfully injected into a human volunteer for the first time. This is a vital step towards a future in which all the blood we need for transfusions can be made in the lab, so that blood donors are no longer essential.
Luc Douay at Pierre and Marie Curie University, Paris, and his colleagues extracted what are called hematopoetic stem cells from a volunteer’s bone marrow. These cells were encouraged to grow into cultured red blood cells using a cocktail of growth factors. After labelling the cells so they could be traced, Douay’s team injected 10 billion – the equivalent of 2 millilitres of blood – back into the original donor to see how they survived.
After five days, 94 to 100 per cent of the cells remained in circulation, while after 26 days, 41 to 63 per cent remained – a survival rate comparable to normal red blood cells. The cultured blood cells also gave every indication of being safe to use: they didn’t transform into a malignant cell type, for example. Instead, they behaved like normal red blood cells, binding to oxygen and releasing it (Blood, DOI: 10.1182/blood-2011-06-362038).
"This is a huge step forward," says Robert Lanza, chief scientific officer at Advanced Cell Technology in Worcester, Massachusetts. In 2008, Lanza was a part of the team that grew red blood cells on a large scale in the lab for the first time.
Anna Rita Migliaccio of Mount Sinai Medical Center in New York City is equally impressed by Douay’s work: "He showed that these cells do not have two tails or three horns and survive normally in the body."
"The results show promise that an unlimited blood reserve is within reach," says Douay. That blood reserve is needed urgently. Although blood donations are increasing in many developed countries, blood banks struggle to keep up with the demands of ageing populations who need more operations – often involving blood transfusions. And a source of HIV-free blood is essential in countries with high rates of HIV infection.
Earlier attempts to create blood substitutes have been disappointing. Several products have been rejected as a result of safety concerns or simply because they didn’t work well (see "The road to artificial blood"). Besides blood derived from stem cells, alternatives include chemical blood – based on the high-oxygen solubility of perfluorocarbons – and oxygen carriers based on haemoglobin, which involve modifications to the red blood cell protein that transports oxygen.
"All aim to mimic, or in some cases enhance the oxygen-carrying ability of the red blood cells normally given as a blood transfusion," says Chris Cooperof the University of Essex in Colchester, UK, who is developing a haemoglobin-based blood substitute that will be genetically modified to reduce its toxicity – haemoglobin is toxic in its unbound state. "The advantage of stem cell technology is that the product will much more closely resemble a red cell transfusion, alleviating some of the safety concerns that continue around the use of the current generation of artificial products," he says.
Thomas Chang at McGill University in Montreal, Canada, says that the success of Douay’s stem-cell approach doesn’t mean research into alternatives is any less worthwhile. Although blood grown from stem cells must be chilled, like fresh blood, "haemoglobin-based artificial blood does not need refrigeration", he says. This stability makes it more useful in remote areas or in the aftermath of natural disasters.
Douay’s next challenge is to scale up production to a point where the cultured blood cells can be made quickly and cheaply in sufficient quantities for blood transfusions. The 10 billion cells his team made wouldn’t go very far – a transfusion typically requires 200 times that number. With his existing technology, Douay estimates that a single transfusion would require 400 litres of culture fluid, which is clearly impractical. "We are still a long way from the vision of dropping a couple of stem cells into the broth and making endless units of blood," says John Hess of the University of Maryland in Baltimore.
Douay believes that it may take several years to scale up the technology. Another possibility is to use embryonic stem cells instead, as Lanza did in 2008. "We can generate up to 100 billion red blood cells from a single six-well plate of stem cells," Lanza says. He also claims to have made red blood cells through yet another technique: generating "induced pluripotent" stem cells from skin samples and coaxing those stem cells into becoming blood cells.
Lanza says he did this using skin from a person with type O blood. People with O negative blood are called "universal donors" because their blood doesn’t trigger an immune reaction in recipients. "This is important for patients with massive blood loss where there isn’t time for blood typing," says Lanza, who hopes to test both types of lab-made blood in people within the next two years