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Published On June 8, 2017

BASIC RESEARCH

Blood Gets an Upgrade

The long search for a blood substitute could take a major step forward this year.

Each year, donors step up to replenish the nation’s blood supply. Depending on volunteers for this critical resource, however, has never been ideal. The units that come in must be screened for diseases—including nascent threats, such as the Zika virus. And what volunteers can supply may not match the demand, especially for people with rare blood-group types and those with conditions that require frequent transfusions (such as sickle cell disease), who can sometimes develop reactions to transfused blood.

Researchers have spent decades searching for a substitute—a form of blood that can be manufactured—with limited success. This year, however, the United Kingdom’s National Health Service Blood and Transplant (NHSBT) organization will sponsor a clinical trial to test a mini-transfusion of red blood cells made from stem cells.

Adult stem cells, isolated from blood donors, are grown in the laboratory to create reticulocytes—young red blood cells. The current trial will look at how well these cells circulate in the bloodstream and whether they perform as well as red blood cells procured by more traditional means. If that first step succeeds, larger amounts of the lab-created blood will be tested in human subjects.

Although stem cell-based methods are promising—the lab is looking at making red blood cells from umbilical cord cells or erythroid cell lines as well—the current culture methods are expensive and inefficient, which makes creating large batches prohibitive.

“Although we can make small doses of blood from stem cells, we still need to develop ways of growing larger amounts of blood more efficiently and more economically,” says Ash Toye, a biochemist at the University of Bristol and a principal investigator at NHSBT, in the United Kingdom.

But the advantages of manufactured blood may involve more than a reliable supply. Cedric Ghevaert, a hematologist and researcher with the NHSBT, says that genome editing can create a more universal blood type. All blood cells carry “ID cards” on their surface, which correspond to the type of blood that’s tolerated in the body. “But genome editing allows us to change the ID card or remove it altogether,” he says. “That way, the cells stay incognito and could be given to anyone without fear of mismatch.”

During the past three decades, a few products have been developed that replicate blood’s principal function, which is to bind chemically with oxygen and carry it throughout the body. Hemopure (approved for use in South Africa and Russia) and MP4, which aimed to transport oxygen to tissue after major blood loss, are used for transfusions to trauma patients. No blood substitute has ever been approved for human use in Europe or the United States.

In another approach, Allan Doctor, critical-care specialist at Washington University School of Medicine in St. Louis, has created a different kind of blood substitute: a powder that he says is easily transportable and can be used in emergency situations. The substitute, called ErythroMer, might be used on the battlefield, in space or after a terrorist attack to keep people alive long enough to get them to a hospital. Though still years away from clinical trials, the powder could potentially meet the need for a blood substitute that can be safely stored until it’s needed. The shelf life of processed blood, when properly refrigerated, is only 42 days. But ErythroMer could last several years.

Meanwhile, Ash Toye, of the NHSBT, still marvels at the natural processes researchers are trying to replicate. “If we could eventually create a system that made blood even a fraction as well as the human body can, but which would also have a more universal donor type, that would be amazing,” says Toye. “The body creates around two million red blood cells a second, from a tiny number of stem cells that live in bone marrow. We just need to develop better ways to replicate the natural process to make more blood more economically.”