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"Artificial blood" test: addressing the need for rare blood types
NHSBT is responsible for blood donation services in England and transplant services across the UK, including managing donation, storage and transplantation of blood, organs, tissues, bone marrow and stem cells, as well as researching new treatments and processes
.
However, NHSBT cannot meet the transfusion needs of a small number of patients with rare blood types, who often have thalassemia or sickle cell anemia in patients who require regular transfusions throughout their lives
.
NHSBT has found that human blood stem cells can induce the production of new red blood cells
in large quantities under laboratory conditions.
If lab-made cells work longer in the body, patients who need blood frequently may not need frequent transfusions, which will reduce iron overload due to frequent transfusions, which can lead to serious complications
.
Therefore, NHSBT hopes to use this technology to provide a new type of blood product for patients with blood needs to meet the needs of patients with rare blood types [1].
In 2021, NHSBT began a first-in-human clinical trial
of red blood cells cultured in the laboratory from adult donor blood stem cells.
The trial is called RESTORE (REcovery and survival of STem cell Originated REd cells).
RESTORE was conducted in the clinical trial room at Addenbrookes Hospital in Cambridge, and the cells used in the trial were manufactured
in NHSBT.
The test is designed to investigate whether lab-grown red blood cells in humans live longer than standard red blood cells [2].
Using a randomized, single-blind, crossover design, RESTORE compares the viability and viability of red blood cells made from CD34+ cells isolated from adult blood with standard donor red blood cells
.
The order in which each subject receives standard or manufactured red blood cells is random, and subjects will not know whether they received standard blood or laboratory-made red blood cells [3].
The researchers first isolated 500,000 stem cells capable of differentiating into red blood cells
with magnetic beads from 470ml of blood from blood donors.
These stem cells are then cultured in the lab for three weeks to grow and develop into 50 billion red blood cells
.
Finally, cells are purified using a standard filter, stored and transfused into the subject
.
At least 10 subjects will receive two mini-transfusions spaced at least four months apart, one with a standard donated red blood cell and one from a lab-grown red blood cell to determine whether the lab-made new red blood cells live longer
than standard red blood cells.
"Artificial blood" is labeled with medical radioactive materials, so scientists can understand how long "artificial blood" survives in the body [4].
So far, two people have been infused with lab-grown red blood cells
.
They are closely monitored, in good health and with no reports
of adverse side effects.
The identities of the participants who have been infusions to date have not been announced to maintain the "blindness"
of the trial.
RESTORE is the world's first time giving red blood cells grown in the lab to another person
as part of a blood transfusion test.
If its safety and effectiveness are proven, lab-made blood cells could revolutionize the treatment of patients with blood disorders, making enough blood
for patients.
The researchers say RESTORE is not intended to replace regular human blood donations, which will continue to account for the majority of
blood transfusions.
But the technology could allow scientists to create very rare blood types that are hard to come by but are crucial
for those who rely on regular blood transfusions for diseases such as sickle cell anemia.
Red blood cells in the blood normally survive in the body for 120 days, after which they age and are replaced
by new cells.
Donated blood contains a mixture of young and aged red blood cells, and blood lifespan cannot be predicted
.
However, laboratories can screen out younger blood cells, and "artificial blood" has a longer lifespan than standard donated blood cells, not only maintaining the expected activity for 120 days, but also surviving longer in the human body, helping patients who need regular blood transfusions to reduce the frequency and volume of blood transfusions, thereby reducing payment costs
.
At present, the cost of "artificial blood" technology is huge
.
With the average cost now around £145 (1,235 yuan) per bag of blood, lab-grown alternatives could be more expensive
, according to NHSBT.
The RESTORE research team did not disclose the cost price of "artificial blood" for the time being, but said that with the development of technology and the expansion of scale, the cost will continue to decrease
.
Human red blood cells need to be stored at 4°C ±2°C for up to 42 days
.
Platelets need to be stored at 22 °C ± 2 °C with a storage period ranging from
24 hours to 5 days.
The short shelf life of platelets poses a challenge
for emergency clinical blood supply.
Manabu Kinoshita, an associate professor at the National Defense Medical College and an expert in immunology, said: "In areas such as remote islands, it is difficult to provide patients with enough blood
.
Artificial blood will be able to save the lives of
patients who would otherwise be unable to save.
”
I still remember that the previously reported Jiangsu Province found only one case of blood type
in the world.
In fact, blood type is a complex concept, including not only types A, B, AB and O, but also rare blood types
such as rh-negative blood.
When patients with rare blood types require blood transfusions, blood origin becomes a problem
.
Laboratory "artificial blood" can knock out cell surface antigens through genetic modification, solving the limitation
of matching on blood sources.
"Artificial blood" does not have a blood type, and patients can avoid the trouble
of blood typing and matching when urgently needed.
Dr Farrukh Shah, NHSBT's medical director, said: "This world-leading research lays the groundwork for laboratories to manufacture red blood cells, which can be safely used for blood transfusions for people with diseases such as sickle cell cells
.
The need for normal blood donations to provide the vast majority of blood will remain
.
But the potential for this work to benefit patients who are difficult to transfuse is enormous
.
”
Dr Rebecca Cardigan, head of NHSBT development and lecturer at the University of Cambridge, said: "We are now able to culture red blood cells to medical grade in order to start this trial
.
We're really looking forward to seeing if they perform better
than standard red blood cells.
”
Professor Ashley Toye, Professor of Cell Biology at the University of Bristol and Head of the Division of Blood and Transplantation at NIHR Red Blood Cell Products, said: "This is the first time that blood has been instilled from an allogeneic donor into a laboratory and is extremely challenging and we are looking forward to seeing how
these cells perform at the end of the clinical trial.
”
Cedric Ghevaert, a professor at the University of Cambridge and consultant with NHSBT, said: "We want lab-grown red blood cells to last longer
than those from blood donors.
If our trial (the first of its kind in the world) is successful, it will mean that patients who currently require regular, long-term transfusions will need fewer transfusions in the future, helping to transform their care [5].
”