A Blog by Jonathan Low

 

Sep 11, 2020

As Covid Depletes Supplies, Scientists Test Lab-Made Blood

Many hospitals began to run out of blood as the coronavirus raged this spring and summer. Red blood cells can be stored for 42 days, platelets for only 5 days. Manufactured blood could exponentially expand the supply and it can be engineered to last longer.

Once the science and testing are completed, the biggest obstacle may be overcoming human resistance to an artificial substance of such importance in their bodies. JL

Nora Eckert reports in the Wall Street Journal:

The spread of Covid-19 and lockdowns (led to) 46,000 blood drives canceled since March, leading to severe shortages. While scientists have developed backups for most parts of our bodies, the production of artificial blood has eluded them. Now, helped by advances in stem-cell research and interest from investors, (a) study aims to assess the safety and efficacy of platelets engineered in a lab out of a special type of stem cell. If successful, the research could pave the way for larger clinical trials and, ultimately, the broad use of lab-made blood.
The patient’s identity and gender are confidential, but his or her blood is at the center of an experiment that could transform medicine. He or she suffers from aplastic anemia, a condition that prevents the patient from producing enough blood cells, including platelets, the tiny cells that help blood clot. The patient also experiences platelet transfusion refractoriness, meaning the body rejects blood from most donors.
At a lab in Kyoto, Japan, scientists are running a pioneering clinical trial to treat this singular patient with a long-sought goal: artificial blood. Led by Dr. Koji Eto and a team at Kyoto University’s Center for IPS Cell Research and Application, the study aims to assess the safety and efficacy of platelets engineered in a lab out of a special type of stem cell. If successful, the research could pave the way for larger clinical trials and, ultimately, the broad use of lab-made blood.
While scientists have developed backups for most parts of our bodies—from prosthetic limbs to titanium teeth implants—the production of artificial blood has eluded them. Now, helped by advances in stem-cell research and interest from investors, scientists are closer than ever to coming up with a blood substitute.
Blood made in a lab could add to the supply from human donors, which can drop dangerously low during natural disasters or pandemics, as the U.S. saw in March. It would also provide a lifesaving remedy for those with blood disorders that prevent them from accepting donations. And it could be quality-controlled for viruses and pathogens in a way that researchers say human samples can’t be.
Today, doctors and surgeons rely on blood donors for transfusions used during surgery, cancer care or following traumatic injuries. The supply must be constantly replenished. Red blood cells can be stored for 42 days, while platelets last only about five days.
The spread of Covid-19 and nationwide lockdowns have exacerbated the problem. Around 46,000 blood drives have been canceled since March due to the need for social distancing, according to the American Red Cross, leading to severe shortages in the spring. If elective surgeries hadn’t been put on pause nationwide, hospitals may have had to stop them to conserve blood, says Chris Hrouda, president of biomedical services at the American Red Cross.
“We were rationing blood to hospitals pretty aggressively,” he says.
Poorer parts of the world struggle even more. Low-income countries have less than one-fifth the number of donors of high-income countries, according to the World Health Organization.
Some religious groups, including the Jehovah’s Witnesses, don’t accept transfusions of donated blood as part of their faith. A representative says blood substitutes may be helpful.
Researchers and companies believe that blood made from induced pluripotent stem cells, or IPS cells, could solve some of these problems by allowing them to manufacture pathogen-free blood that would be accepted by nearly all patients.
Dr. Eto’s study, which began in March 2019 and ends in early 2021, is one of a number slated to take place over the next year. It uses blood grown from the patient’s own cells, meaning the person’s body will hypothetically accept it.
Dr. Cedric Ghevaert, a Cambridge University hematologist, is leading a National Health Service-funded study on lab-grown red blood cells, the part of blood that transports oxygen through the body. The trial on 20 healthy volunteers was put on hold in March because of the pandemic. The researchers hope to prove that red blood cells grown from stem cells last longer in circulation than natural red blood cells, Dr. Ghevaert says.
Megakaryon, a Japanese company creating blood products from stem cells, advised by Dr. Eto, is preparing for a 2021 clinical trial to treat patients with low platelet counts.
Massachusetts-based PlateletBio received a contract from the Biomedical Advanced Research and Development Authority, or Barda, part of the Department of Health and Human Services, worth up to $56 million to develop cells functioning as platelets for victims of nuclear or radiological attacks. The company hopes to enter clinical trials by the end of 2021, says company CEO Dr. Sam Rasty.
The field of cell therapy “has started to explode over the last few years,” Dr. Rasty says. “Investors are significantly interested in it, certainly from a medical unmet-need perspective.”

Dr. George Daley, the dean of Harvard Medical School, whose lab studies how stem cells can be used as therapies, saw the nation shift its concern to the safety of the blood supply during the HIV/AIDS epidemic. Virus outbreaks such as Zika, Ebola and Covid-19 have further underscored the need for clean blood donations.
“There’s always a worry about new infections that can contaminate the blood, again, raising the value and importance of being able to more carefully control the manufacture and presentation of blood through a different system,” says Dr. Daley.
Over the decades, scientists have tested everything from milky fluids to freeze-dried blood powders. A revolution in the field came in 2006, with the discovery of IPS cells. Dr. Shinya Yamanaka discovered four genes that, when inserted into a mature, nonembryonic cell, would turn it into this special kind of stem cell. The resulting IPS cell could then turn into almost any kind of cell in the body, including red blood cells and platelets, and multiply. The method provided the key to making artificial blood: the ability to manufacture a vast bank of cells and, with that, to scale the production of lab-made blood.

The Nobel Prize-winning technology also sent scientists back to the drawing board to make use of this new tool—like re-engineering car engines with electricity after decades of using gas engines, Dr. Ghevaert says.
Making blood in a lab is expensive. Manufacturing a bag of platelets can cost up to $1 million. Hospitals currently pay roughly $500 for a bag of donated platelets, according to a 2017 National Blood Collection and Utilization survey. Labs that have managed to scale the technology, such as Dr. Eto’s, have seen a decrease in cost, but still spend tens of thousands of dollars on bags of platelets. A typical transfusion takes one bag of platelets but can easily require more, according to Dr. Leslie Silberstein, director of the division of transfusion medicine at Boston Children’s Hospital.
With enough funding, a system of blood factories could one day support the national supply in emergencies, scientists say, though donations would still be the main source.
Dr. Ghevaert envisions a collection of factories, complete with vast stirring tanks, freezers to chill batches for transport, and secondary processing plants where platelets are produced. The cells could be trucked or flown to areas most in need, such as the developing world or a city hit with a natural disaster.
“‘Charlie and the Chocolate Factory,’ but applied to platelets? I think there’s no question such a thing will exist,” he says.