With the first participants now taking part, we look at the RESTORE clinical trial, which it is hoped will lead to a revolution in treatments for people with blood disorders.
The world-first clinical trial in which red blood cells that have been grown in a laboratory and transfused into another person is now underway.
The manufactured blood cells, which were grown from stem cells from donors, are being transfused into volunteers in the RESTORE randomised controlled clinical trial.
If proved safe and effective, manufactured blood cells could in time revolutionise treatments for people with blood disorders, such as sickle cell and rare blood types. It can be difficult to find enough well-matched donated blood for some people with these disorders.
The RESTORE trial is a joint research initiative by NHS Blood and Transplant (NHSBT) and the University of Bristol, working with the University of Cambridge, Guy’s and St Thomas’ NHS Foundation Trust, the National Institute for Health and Care Research (NIHR) Cambridge Clinical Research Facility and Cambridge University Hospitals NHS Foundation Trust. It is part-funded by an NIHR grant.
The first participant
Yvonne Smith, 69, from near Bury St Edmunds in Suffolk, became one of the first of two people to receive red blood cells in the trial.
Yvonne was previously a blood donor, making about 60 donations, but is no longer able to donate after a case of breast cancer in 2014. She said: “I thought ‘what else can I do?’ I ticked a box and put my name forwards for research.”
The trial details
RESTORE is a clinical trial initiated by a joint research unit from NHS Blood and Transplant and the University of Bristol called the NIHR Blood and Transplant Research Unit in Red Blood Cell Products.
The unit is 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.
The red blood cells are grown at NHSBT’s Advanced Therapies Unit in the Cellular and Molecular Therapies function in Filton from blood donors who have agreed to take part in the study.
The cells are labelled with a tracer element by the Radiopharmacy Unit at Guy’s and St Thomas’ Hospital so they can be tracked through the recipient’s body when they are transfused.
The study has a randomised, single-blind, cross-over design and the order in which each recipient receives the standard or manufactured red blood cells is randomised and recipients will be blinded to that order.
Co-Chief Investigator Cedric Ghevaert, Professor in Transfusion Medicine and Consultant Haematologist at the University of Cambridge and NHS Blood and Transplant, explained: “This clinical trial is groundbreaking because it is the first time we are producing red cells in the laboratory in such a way we can compare how they behave after transfusion compared to standard donated red cells. We are immensely grateful to our trial participants. Without them, this clinical trial would never see the light of day.”
How the trial works
The trial is a study of the lifespan of the lab-grown cells derived from CD34+ cells compared with infusions of standard red blood cells from the same donor. The lab-grown blood cells are all fresh, so the trial team expects them to perform better than a similar transfusion of standard donated red cells, which contains cells of varying ages.
Additionally, if manufactured cells last longer in the body, patients who regularly need blood may not need transfusions as often. This would reduce iron overload from frequent blood transfusions, which can lead to serious complications.
The trial is the first step towards making lab-grown red blood cells available as a future clinical product. For the foreseeable future, manufactured cells could only be used for a very small number of patients with very complex transfusions needs.
The amount of lab-grown cells being infused varies, but is around 5–10 mls.
Donors were recruited from NHSBT’s blood donor base. They donated blood to the trial and stem cells were separated out from their blood. These stem cells were then grown to produce red blood cells in a laboratory at NHSBT’s Advanced Therapies Unit in Bristol. The recipients of the blood were recruited from healthy members of the NIHR BioResource.
A minimum of 10 participants are receiving two mini transfusions at least four months apart – one of standard donated red cells and one of lab-grown red cells, to find out if the young red blood cells made in the laboratory last longer than cells made in the body.
“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”
Clinical use
Further trials are needed before clinical use, but this research marks a significant step in using lab-grown red blood cells to improve treatment for patients with rare blood types or people with complex transfusion needs.
Professor Ashley Toye, Professor of Cell Biology at the University of Bristol and Director of the NIHR Blood and Transplant Unit in red cell products, says: “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.”
Chief Investigator Professor Cedric Ghevaert, Professor in Transfusion Medicine and Consultant Haematologist at the University of Cambridge and NHSBT, says: “We hope our lab-grown red blood cells will last longer than those that come from blood donors. If our trial, the first such in the world, is successful, it will mean that patients who currently require regular long-term blood transfusions will need fewer transfusions in future, helping transform their care.”
Dr Farrukh Shah is the Medical Director of Transfusion for NHS Blood and Transplant. He says: “Patients who need regular or intermittent blood transfusions may [as a] result develop antibodies against minor blood groups, which makes it harder to find donor blood that can be transfused without the risk of a potentially life-threatening reaction.
“This world-leading research lays the groundwork for the manufacture of red blood cells that can safely be used to transfuse people with disorders like sickle cell.”
He adds: “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.”
Image credit | iStock| Alamy
