Efforts to develop lab-grown blood cells for blood transfusions may soon materialize. Since 2021, the National Health Service (NHS) in the United Kingdom has been working on RESTORE— a project dedicated to growing red blood cells from stem cells. The RESTORE project aims to develop an alternative blood transfusion treatment that is more effective than using donor blood and that minimizes the number of transfusions that patients with blood diseases must receive in their lifetime.
Now, RESTORE’s lab-grown red blood cells are the first in the world to have entered clinical trials for blood transfusions, marking a significant milestone for the NHS.
Since the pandemic, the national blood supply level has significantly decreased according to America’s Blood Centers Organization. More than half of the United States’ community blood centers have a shortage of blood donations. This shortage has affected blood centers in the nation so much that many centers have blood supplies that will only last them a couple of days at a time, if not less.
This is an especially dire situation considering that in an average year, 4.5 million Americans require blood transfusions. In addition, a subset of the population suffers from blood diseases that require them to receive multiple blood transfusions within a year. Particularly, those who suffer from blood diseases like thalassemia or sickle cell disease.
People who suffer from thalassemia or sickle cell disease have red blood cells that are unable to carry oxygen. A lack of oxygen-rich blood can cause damage to the nerves and organs. If left untreated, the depletion of oxygen in the blood and organs is fatal. One of the primary treatments for patients with these diseases is red blood cell transfusions. This procedure increases the number of normal red blood cells that carry oxygen through the body.
While blood transfusions are relatively safe and standard, patients that suffer from blood diseases and produce minimal healthy red blood cells are often required to receive regular blood transfusions throughout their lifetime just to stay healthy. Unfortunately, the process of receiving multiple blood transfusions over time introduces greater risks and can be dangerous for patients.
The biggest challenge for those receiving blood transfusions is the difficulty of finding donor blood that is a good match for each patient. If patients are given blood that is incompatible with their body, the immune system may attack the new blood and cause serious health problems. An additional challenge is that patients who receive regular blood transfusions during their life run the risk of receiving an overload of iron. This can also cause additional serious health complications.
Due to the potential health risks of blood donor-based transfusions along with the current blood donor shortage, there exists a need to develop alternative sources of blood that are more reliable and that last longer in the body.
One way to address these needs is through stem cells. Stem cells are unique in that they can be reverted to earlier stages of cellular development. When stem cells are reverted to their embryonic state and given the correct chemical signals, they can grow into nearly any other type of adult cell in the body. This includes red blood cells.
Studies have found that while manufactured cells function like normal cells, they are more likely to survive longer in the body than cells from a donor. Researchers at the NHS speculated that by manufacturing red blood cells and successfully transfusing them into patients, the lab-grown cells would survive longer in the body and decrease the number of transfusions that patients need within their lifetime.
By using stem cells instead of blood donors, researchers can also develop blood supplies for patients with hard-to-match blood types. Since stem cells taken from a patient contain genes that are unique to the patient, healthy red blood cells created from a patient’s own stem cells are much less likely to be rejected by the body.
While the RESTORE project is in its early clinical stages and has not published its procedure for red blood cell synthesis, other studies have relied on hematopoietic stem cells. Hematopoietic stem cells are rare, immature cells that have the potential to develop into any type of blood cell. This includes white blood cells, platelets, and red blood cells. Hematopoietic stem cells are found both in the blood and in the bone marrow.
In a procedure published in 2020 by the journal Stem Cell Research and Therapy, researchers produced red blood cells from hematopoietic stem cells in 3 steps and over a 21-day period.
The stem cells were collected and sterilized from healthy donors before being isolated from the blood. After isolating the stem cells, they were placed in a bath of human blood plasma, insulin, and a solution containing iron and transferrin protein. Transferrin is a protein that helps blood cells absorb iron. The second step involved adding a compound called erythropoietin. Erythropoietin is a glycoprotein that supports the transformation of hematopoietic stem cells into other blood cells. Finally, in the third step, the cells were supplemented with additional chemicals to promote the growth of red blood cells.
While procedures like this one are accepted methods to produce red blood cells, the fact that the process takes 21 days may prevent hematopoietic stem cell-based red blood cells from being a realistic solution for clinical applications.
Despite this, the RESTORE project is still motivated to test lab-grown red blood cells in a clinical setting. As of now, two people have been transfused with RESTORE’s lab-grown red blood cells. The two participants were given a micro-transfusion of about one to two teaspoons of manufactured cells. Excitingly, the participants have not exhibited any adverse side effects from the transfusion.
As clinical trials continue, the NHS plans on testing the lab-grown cells on a minimum of ten participants. Each participant will receive one micro-transfusion of regular donor-based red blood cells and one micro-transfusion of lab-grown cells. These transfusions will be staged at least four months apart to allow researchers to determine whether the lab-grown cells last longer in the body than donor-based red blood cells.
Overall, much more research is required to determine if greater dosages of stem cell blood similarly do not cause adverse reactions in patients. Typically, blood transfusions require approximately a pint of blood. So far, the RESTORE project has only attempted to transfuse micro dosages of lab-grown blood. Until we know how patients respond to greater quantities of blood, it is difficult to determine whether lab-grown red blood cells are a viable alternative for patients needing regular blood transfusions. However, these initial clinical trials are a world-first and optimistic step towards safer and more effective treatments for those suffering from blood diseases.