Artificial blood: the quest for one of science’s holy grails – Stat – STAT

S

T. LOUIS When red blood cells are poured into the test tubes here in Dr. Allan Doctors lab, tiny tools measure the reaction of the rabbit aortas strung up inside, computing if and how strongly the aortas constrict. Doctor and his team are trying to make sure that when they dump in the artificial blood theyre developing, the aortas react the same way.

The experiments being conducted on a recent day were not only just a few of the many the team will need to run before testing their blood substitute in people, but were also early steps to show that their design, with any luck, can steer them beyond the decades of failure in the field.

There has been about 50, 60 years of research in trying to make a blood substitute that has not worked, said Doctor, a pediatric critical care physician and researcher at Washington University in St. Louis.

article continues after advertisement

The need for such a product is clear. Blood loss from traumatic injuries is responsible for thousands of deaths annually, and even when people survive, oxygen depletion can leave tissue permanently injured. Fresh blood can only be stored for 42 days, and only lasts for a few hours unrefrigerated. A substitute could be vital in settings like battlefields or rural areas without easy access to blood, used as a stopgap measure to keep the injured alive until they get to a hospital.

But the quest to develop substitute blood has bedeviled researchers in academia, the military, and the biopharma industry, with several companies including Baxter, Northfield Laboratories, and Biopure abandoning theirattempts.

The artificial blood researchers have been trying to cook up is not a true substitute, in that it wouldnt perform all of bloods functions, but rather provide a means to deliver oxygen throughout the body.

One key problem: Hemoglobin, the protein in red blood cells that carries oxygen from the lungs to needy tissues, can damage tissue and cause blood vessels to constrict. Thats one reason why hemoglobin is contained in cells to isolate it and its toxic iron.

Any successful blood substitute will need to transport and deliver oxygen, while staving off the threat hemoglobin poses.

In past attempts, scientists have tried to tweak hemoglobin to make it safer, but so far, no blood substitute has been approved for use in the United States or Europe. (One substitute, Hemopure from HbO2 Therapeutics, is used in South Africa, and a clinical trial of a stem cell-based substitute is expected to begin this fall in the United Kingdom.)

But instead of trying to engineer hemoglobin, Doctor and his colleagues have encased it in a synthetic polymer designed by one of Doctors collaborators, Dipanjan Pan of the University of Illinois, Urbana-Champaign.

They hope the case will ensure that their substitute blood, called ErythroMer, wont cause a tightening in the blood vessels, whichincreases the risk of heart attack and stroke.

At the same time, ErythroMer detects where oxygen should be delivered based on the pH level of the blood, moving oxygen from the lungs to where its most needed like a junkyard magnet picking up a car in one spot and dropping it elsewhere.

If its successful, ErythroMer could be freeze-dried into a powder and stored safely for years, so that when its needed, it can be mixed with sterile water and administered. Its designed to be immune silent so that the immune system doesnt attack it and it could be given to people of any blood type.

Scientists not working on ErythroMer said it appears to be an improvement in some respects over earlier candidates, but note that it is not the first to attempt enclosing hemoglobin in various materials. So far, no one has cracked the code of creating an artificial blood, and its not clear this group will either.

Its not as easy as it sounds, said Dr. Ernest Moore, the vice chair of trauma and critical care research at the University of Colorado, Denver, who has helped run clinical trials of other substitutes.

One concern for Mark Scott, a senior scientist at Canadian Blood Services, is the tininess of ErythroMer. Each particle is about one-fiftieth the size of a normal red blood cell, and Scott said that increased the risk that it could leak from the bloodstream into surrounding tissue. And when someone loses a lot of blood and goes into shock, their blood vessels only become more leaky, Scott said.

Pentagon hopes to use foam, injected through belly button, to save bleeding soldiers

These are all things that you really have to be concerned about, said Scott, who also works at the Center for Blood Research at the University of British Columbia. Is the size going to lead to a lot of vascular leakage? Is the hemoglobin thats inside the shell stabilized so it wont cause acute or chronic toxicity?

One advantage of the small size of the substitute blood, both Scott and Doctor said, is that it could be used for people with sickle cell disease. During sickle cell crises, the misshapen red blood cells gum up blood vessels, and its possible that ErythroMer could get around the logjams and deliver oxygen past those points. Doctor also raised the idea that it could be used to oxygenate organs during transplant operations.

In addition to overcoming the biological hurdles, the ErythroMer team will eventually have to convince regulators that itsproduct is safe enough to test in people (depending on its success in animals, that is). Several scientists said the Food and Drug Administration seems hesitant to green-light new trials of blood substitutes and some said rightfully so because of safety concerns from past products. Plus, clinical trials of trauma-related treatments often run into ethical quandaries about informed consent.

In an email, an FDA spokeswoman said that studies on these types of products have found they are not safe or effective, but that the agency recognizes they potentially could be lifesaving in situations where blood transfusion is necessary, but blood is not available or cant be used. She said future clinical studies remain possible.

Still, human studiesare a long ways away, the researchers acknowledge. So far, Doctor and his team, whose work has been supported by the Department of Defense, have presented results from rodent studies at a scientific conference. And they have their own questions about how ErythroMer will perform as they test it in larger animals, first in rabbits: Does it damage other cells in the bloodstream? Does it interfere with the clotting process?

The team has formed a company called KaloCyte (Greek for good cell) to make the substitute for further studies. Doctor likened it to moving the production from a craft brewery scale so far, Doctor said, its been lovingly made by graduate students, batch by batch to the scale and standards of another St. Louis blend, Budweiser.

Andrew Joseph can be reached at andrew.joseph@statnews.com Follow Andrew on Twitter @DrewQJoseph

Read more:
Artificial blood: the quest for one of science's holy grails - Stat - STAT