Laboratory-grown red blood cells have been transfused into a human recipient for the first time. This gives hope to patients with blood diseases that require frequent blood transfusions.
In the RESTORE randomized controlled clinical trial, two participants were infused with around 5-10mls — about one to two teaspoons — of the lab-grown red cells. Both were closely monitored and no untoward side effects were reported.
Red blood cells (RBC) are made in the bone marrow and found in the blood. They contain a protein hemoglobin, which is responsible for carrying oxygen from the lungs to all body tissues.
Blood donors were recruited from the UK’s National Health Service Blood and Transplant donor base. They donated blood to the trial and stem cells were separated from their blood. These stem cells were then grown to produce red blood cells in a laboratory.
Ashley Toye, Professor of Cell Biology at the University of Bristol and Director of the NIHR Blood and Transplant Unit in red cell products, said in a press release: “This challenging and exciting trial is a huge stepping stone for manufacturing blood from stem cells. This is the first-time lab-grown blood from an allogeneic donor has been transfused and we are excited to see how well the cells perform at the end of the clinical trial.”
Why is it significant?
Tumas Beinortas, an academic clinical fellow at the University of Cambridge, who is not involved in the study, says the transfusion is significant because it is the first clinical step in an effort to create blood from stem cells outside of the living human body.
“The average lifespan of the red blood cells is 120 days. When a person receives a blood transfusion from donated blood, red blood cells are of varying ages. The lab-made blood is fresh, so it is expected to last longer in a human than conventional red blood cells. Therefore, patients may not need transfusions as often,” Beinortas says.
The technology could significantly improve the care of people with diseases that require frequent red blood cell transfusions, such as beta-thalassemia, sickle cell disease, or myelodysplastic syndromes.
“These patients may require blood transfusions every few weeks. Another big issue is a process called alloimmunization, when a person's immune system starts producing antibodies against the transfused blood cells. Finding donors for such patients is extremely difficult.
Another significant issue is finding blood for people with rare blood groups — there is simply a very narrow potential donor pool for them. Giving mismatched blood can readily lead to alloimmunization. Red blood cells produced in vitro would readily address alloimmunization and rare donor issues,” Beinortas told Healthnews.
Beinortas says there are risks associated with frequent blood transfusions, such as iron overload, when excess iron is stored in the liver, joints, pancreas, and heart. In rare cases, iron overload can severely damage internal organs.
How are blood cells made?
In the distant future, Beinortas says, this technology may completely replace the necessity for human blood donation for red blood cell fraction. However, he emphasizes that producing blood in vitro at scale is probably decades away.
“Creating red blood cells in vitro from stem cells required finding serial combinations of proteins called growth factors that initially keep a portion of stem cells alive while making others differentiate through multiple stages until they become functional red blood cells.
In order to achieve a meaningful amount of red blood cells, big incubation vessels are required. In the final stages, red blood cells are fractionated from the rest of the media by centrifugation. The last stage of production is quality control that ensures there are no infectious agents in the blood, such as viruses or bacteria, before it is packaged for transfusion,” Beinortas says.
The study authors say that for the foreseeable future, manufactured cells could only be used for a very small number of patients with very complex transfusion needs.
The RESTORE trial is a joint research initiative by NHS Blood and Transplant and the University of Bristol, working with the University of Cambridge, Guy’s and St Thomas’ NHS Foundation Trust, NIHR Cambridge Clinical Research Facility, and Cambridge University Hospitals NHS Foundation Trust.