Embryonic Stem Cells Used to Generate O-negative Blood

by Gopalan on Aug 20 2008 11:43 AM

US scientists say they have used embryonic stem cells to generate type O-negative blood, a rare blood type prized by doctors for its versatility.

The research team outlined a four-step process for turning embryonic stem cells into red blood cells capable of carrying as much oxygen as normal blood. The procedure was published online by the journal Blood.

The ability to make blood in the lab would guarantee that hospitals and blood banks have access to an ample supply of all types of blood, including the rare AB-negative and the universal donor type, O-negative.

It would also ensure that patients are never at risk of contracting diseases such as hepatitis C or HIV from donor blood, said Dr. Dan Kaufman, associate director of the University of Minnesota's Stem Cell Institute, who wasn't involved in the study.

"People don't usually think about these types of cells when they talk about human embryonic stem cell therapy, but it is important," Kaufman said. "There's more infections all the time, and the number of donors is more and more limited."

Researchers have tried to harness the so-called adult stem cells that are responsible for making blood in the body, but their methods were far too inefficient to be put to practical use, experts said.

In the new study, researchers were able to make as many as 100 billion red blood cells -- enough to fill two or three collection tubes -- from a single plate of embryonic stem cells.

After allowing the stem cells to begin the earliest stages of embryonic development, the researchers prompted some of them to grow into red blood cells by exposing them to a variety of proteins.

Up to 65% of the resulting cells matured to the point at which they shed their nucleus, which allows them to take on the distinctive doughnut shape of circulating red blood cells, said Dr. Robert Lanza, chief scientific officer at Advanced Cell Technology Inc. and the study's senior author.

"We literally generated whole tubs in the lab, from scratch," said Robert Lanza, Chief Scientific Officer at Advanced Cell Technology and Adjunct Professor at Wake Forest University School of Medicine, North Carolina.

People usually require blood transfusions that match their own blood type: A mismatch can be fatal. Type O-negative can be safely transferred into anyone, but is only possessed by about 7 percent of the population, leaving supplies perpetually short.
The new technique, devised by Lanza and colleagues at the Mayo Clinic and University of Illinois, is still preliminary. Its safety hasn't yet been proved in animals, much less humans.

But because blood cells are short-lived and cannot divide, there's reason to believe that stem cell-derived blood cells could pose fewer complications than other therapeutic stem cells, which can divide unpredictably, writes Brandon Keim on Wired.

"The beautiful thing is that you start with one line, expand them indefinitely and generate as many as you want," said Lanza. "It's a literally inexhaustible source of cells for therapy."

Lanza's team allowed a small culture of embryonic stem cells -- naturally capable of becoming any other type of tissue in the body -- to divide until it numbered a few billion cells. These they treated with a chemical cocktail that coaxed the cells into becoming type-O negative blood.

Tests showed the blood cells to be identical to each other, and able to carry oxygen as efficiently as their natural counterparts.

The Red Cross described the work as "pioneering." However, they warned against premature celebration.

"At this stage, the work is very promising, but has not progressed to the stage where the cultured cells are fully equivalent" to natural cells, said the organization in a statement. "Much more work will yet be needed before this becomes a practical reality."

The most pressing uncertainty is safety: Embryonic stem cells are sometimes unpredictable and can develop genetic mutations during chemical reprogramming, leading to future side effects.

Blood cells, however, don't have any DNA -- they lose their nuclei as they develop from stem cells -- and don't divide, instead being broken down by the body when their four-month life cycle ends. That, said Lanza, should reduce the possibility of complications.

"You don't have to worry about anything lifelong," he said. "They'll be gone no matter what."

The ethics are potentially problematic, as embryonic stem cells ultimately originate in an embryo that is destroyed during their harvest -- a process that some religious conservatives equate with murder.

But Lanza said his technique could also work with stem cells produced by de-differentiation, a new and ethically trouble-free process during which adult cells regress into an embryonic state.

De-differentiated cells have a tendency to go cancerous -- but because blood cells are DNA-free, said Lanza, they could be safe in this particular application.

If Lanza's technique works, it will be a boon wherever blood transfusions are needed, but especially in places where type O-negative blood is not immediately available, such as emergency rooms and battlefields.

"There's always a great demand for type O blood," said Red Cross spokeswoman Molly Dalton. "It's always a worry that we don't have enough."

However, Roger Dodd, director of the American Red Cross' Holland Laboratory in Rockville, Maryland, said that producing blood in the lab could cost thousands of dollars per unit -- far too expensive to replace the 14 million pints of red blood cells that are transfused every year. "It's a rather ambitious goal," Dodd said.