It began with mere teaspoons of blood. But if everything goes right, this investigational therapy could scale up to whole units.

Across the Atlantic, UK researchers have embarked on an experiment with revolutionary potential: lab-grown blood for use in transfusions.

 

Inside the investigation

This investigation is called the RESTORE trial and it’s breaking new ground, as reported in an article published by NHS Blood and Transplant.

First ever clinical trial of laboratory grown red blood cells being transfused into another person. NHS Blood and Transplant. November 7, 2022.

For what is believed to be the first time, researchers have grown red blood cells in a lab and then transfused them into a live recipient.

 

There is a known stem cell system, the CD34+ hematopoietic stem cell, that is employed in bone marrow research enabling the cells to self-renew and produce mature blood cells, such as erythrocytes, leukocytes, platelets, and lymphocytes, using CRISPR technology.

Who is hematopoietic stem cell: CD34+ or CD34-? Int J Hematol. 1999;70(4):213–215.

 

Two recipients received between 5 ml and 10 ml of the lab-grown blood, which was derived from donor stem cells. As of November 7, 2022, the two recipients, whose identities were withheld, had experienced no adverse events.

The National Health Service Blood and Transplant (NHSBT) recruited donors from its database. Their stem cells were separated from their donated blood and then grown in a laboratory. The recipients—all of whom had no underlying health conditions—were recruited from the National Institute for Health and Care Research BioResource.

Plans call for the RESTORE trial to include a minimum of 10 participants, all of whom will receive two of these small transfusions with 4 months in between. The first donation will be with conventional red blood cells, while the second donation will include lab-grown red blood cells.

 

Cell lifespan to be watched

In addition to determining safety and efficacy, the RESTORE trial will also assess one other critical variable: donor cell lifespan, according to the NHS Blood and Transplant article.

Researchers speculate that lab-grown cells may have a longer lifespan since they are a uniform age and are fresh. By comparison, conventional donor cells are of varying ages.

“What we’re hoping is, because they’re so freshly made and ready to go, they’ll be better,” said Ashley Toye, PhD, professor at the University of Bristol and NHSBT research unit in a video report on BBC's “The Health Show.” Dr. Toye added that if this proves to be true, it would be the first time that blood cells have been taken from a donor and put into an unrelated volunteer.

The UK study labeled the modified stem cells with a radioactive tracer, and the lifespan can be monitored through cell destruction.

The only other time this has been done in the past is where it’s been taken from a person and gone back into that person. So now we’ve taken it a step further.

“We’ve taken it from a donor that’s not related,” Dr. Toye said. “That donor has produced blood. And then it’s gone into somebody unrelated and effectively, that’s a world first. That’s called an allogeneic transfusion.”

If this technology is proven to be safe, effective, and scalable, it could be a game-changer for patients who regularly require blood transfusions. A longer cell lifespan would mean fewer transfusions for these patients.

 

Easing the disease burden

This would be most-welcome news for people with sickle cell disease.

The CDC estimates that there are about 100,000 Americans with sickle cell disease, which predominantly affects people with sub-Saharan African ancestry, or people from Spanish-speaking parts of the Western Hemisphere, as well as people from Saudi Arabia, India, and some Mediterranean countries.

Data & statistics on sickle cell disease. Centers for Disease Control and Prevention. Updated May 2, 2022.

These patients all face a high disease burden.

 

A 2022 BMC Pediatrics study sought to assess the burden of chronic transfusion therapy (CTT) for patients and their families.

Hawkins LM, Sinha CB, Ross D, et al. Patient and family experience with chronic transfusion therapy for sickle cell disease: A qualitative study. BMC Pediatr. 2020;20(1):172.

The researchers interviewed 15 parents of children under the age of 18, and 9 children aged between 12 and 18. All of the children had sickle cell disease and had been receiving CTT for more than a year.

 

The researchers identified common themes among the patients, who reported a high disease burden associated with CTT. That burden included venous-access distress, difficulty with chelation therapy, and anxiety about complications from CTT.

We found that patients and families experience substantial burdens of care and challenges in balancing demands of work, school, and other life activities with CTT, though they recognize the importance and benefits of CTT.

In addition to the convenience factor of fewer transfusions, lab-grown red blood cells could also lower certain transfusion risks for people with sickle cell disease. Fewer transfusions would lessen the risk of iron overload, which could stem from the many transfusions sickle cell disease patients receive, according to research published by StatPearls.

Mangla A, Eshan M, Agarwal N, et al. Sickle cell anemia. StatPearls. National Library of Medicine. Updated May 14, 2022.

 

Hepatic cirrhosis occurring from excess iron is a leading cause of death among sickle cell disease patients.

Also, repeated transfusions can lead to alloimmunization linked to repeated exposure to alloantigens in units of donor blood, according to research published by Frontiers in Medicine.

Conrath S, Vantilcke V, Parisot M, et al. Increased prevalence of alloimmunization in sickle cell disease? Should we restore blood donation in French Guiana? Front Med. 2021;8:681549.

This can lead to delayed hemolytic transfusion reactions and restrict future transfusion. Fewer transfusions would also potentially avoid this adverse effect.

 

 

Looking ahead

Of course, all of this is a long way off. Additional research is required before lab-grown red blood cells see clinical use—if they are determined to be safe and effective.

The RESTORE researchers said in the NHS Blood and Transplant article that for the foreseeable future, lab-grown red blood cells may only see use in a small group of patients with “very complex transfusion needs.”

Other, related studies are also underway. One example is a similar study being conducted in the US attempting to use CD34+ hematopoietic stem cells for patients with transfusion-dependent beta-thalassemia.

A safety and efficacy study evaluating CTX001 in subjects with transfusion-dependent β-thalassemia. ClinicalTrials.gov. Updated December 1, 2022.

 

Such intriguing research does raise the prospect of hope. But, according to Dr. Farrukh Shah, MBBS, medical director of transfusion for NHS Blood and Transplant, the immediate need for standard blood transfusion—and the donations that make it possible—persists.

The need for normal blood donations to provide the vast majority of blood will remain, but the potential for this work to benefit hard-to-transfuse patients is very significant.