“This technology gives us that particular dream, or at least it brings us a lot closer,” said Klein.
There will be blood
To ramp up production, the UK researchers infected stem cells with cervical cancer genes. By inserting cancer genes from human papilloma virus (HPV) into bone marrow cells, Frayne and her colleagues were able to create the first adult red blood cells that could multiply an infinite number of times. These cells are referred to as “immortal.”
As the red blood cells mature, they spit out the nucleus — the core that houses their DNA — giving the cells a signature round, dimpled shape. Frayne and her colleagues filtered those cells from the rest, so the final batch did not contain the active cancer genes.
Frayne said that a small number of these stem cells can be found in a simple blood draw, too; there’s no need to do an invasive biopsy of the bone. Since her team completed the study last year, she said, they have already created two new immortal cell lines this way.
But his cells didn’t eject the nucleus well enough, and fetal blood cells have too tight a grip on oxygen; they are less likely to drop off the oxygen where it needs to go. Eventually, though, he abandoned the research because “it’s not really commercially viable.”
Many others have attempted to create blood in the lab, using stem cells from umbilical cords and other sources. But these stem cells fizzle out and stop dividing at a certain point.
“It’s almost like they desperately want to carry on differentiating” into mature cells, Frayne said.
Frayne said that the first human trials will begin in England later this year, though they will not be using the immortal cells from her new study. Making the new cells under industry standards, Frayne said, could take at least several more years.
But where Lanza really expects to see this technology is on the battlefield.
Red blood sells
Lanza, who met with DARPA officials about his own blood cell research in the past, said that the military wants to use lab-grown blood “for patients who have massive blood loss, particularly in the battlefield, where a soldier is blown up by a bomb and there isn’t time for blood typing.”
“I think the goal ultimately is to put this on the back of a Humvee,” he said.
That research, however, met the same obstacles other scientists faced in the past, Klein said.
“They were not able to make sufficient amounts blood at any kind of reasonable cost,” said Klein, who also serves on the FDA Blood Products Advisory Committee. Though familiar with the DARPA research, he was not involved in evaluating its products.
“To make big huge vats of it would be outside of our ability in a research lab,” she said. “We’d have to have company interest.”
A hospital in the US might pay hundreds to thousands of dollars to purchase and test a unit of donated blood, and it may charge far more to transfuse it to patients. Producing a pint of blood using her method, Frayne said, would likely be several times more expensive than buying bags from blood donors in the UK.
But Frayne is optimistic that costs will come down. She hopes that lab-grown cells will be shown to last longer, and therefore doctors might need to use less blood less frequently. That’s because stem cells can be collected while they’re young, Frayne said, while human blood has cells of all different ages. Many donated blood cells die not long after transfusion.
That aside, Klein said that lowering the cost to $1,000 to $2,000 per unit of blood would make these cells worth the price for a small subset of patients who have rare blood types or need regular transfusions. For the typical hospital patient, however, it would probably not be very practical or cost-effective, he said.
But it is their willingness to invest money in the research, Klein said, that may have led to the British team’s success where the US and other countries have faltered.
“They have put a great deal of financial muscle behind doing this on a national basis, which we simply haven’t seen in the United States,” he said, adding that perhaps there was an element of “healthy skepticism (in the US) that maybe it will never in our lifetime be practical.”
“I don’t share that skepticism,” he said.
But what about the rogue red cell that slips through the filter with its cancer genes still intact? Lanza calls these cells “escapees.”
“When you’re dealing with such huge numbers of cells,” said Lanza, “there may be a few of these cells that would slip in.”
Frayne said that these cells are highly unlikely to cause any form of blood cancer. The cancer genes are only switched on by a certain antibiotic, and by the time the cells are collected, any remaining nuclei are no longer working. Before blood transfusion, radiation can also be used to destroy any leftover DNA without affecting normal cells, she said.
Still, Frayne said, “These are all really good points to be raising, and they need to be looked at.”
But none of these concerns have slowed a deluge of requests to use her cells, Frayne said, though perhaps not from whom you’d expect. It’s not blood banks hoping to capitalize on a new, if untested, method. In fact, it’s other researchers who, until now, have not had an unlimited way to study diseases like malaria, which infect red blood cells. “That’s where all my requests are coming from,” she said.
Klein, Lanza and Frayne all said lab-grown blood cells are not meant to replace blood donors. To fill a national blood service, or even a single hospital, will require another major leap in the research.
“They’re not going to put the Red Cross out of business,” said Lanza. “Volunteer blood donations are always going to be the first line of defense — but with this technology, you have a safety net.”