By: John Ortiz, PharmD Candidate c/o 2025

What is a Blood Transfusion?

A blood transfusion is a procedure where donated blood is intravenously administered to a patient. Generally, it is used to treat patients who are experiencing blood loss or a deficiency of integral blood components. In the United States, there are 21 million blood transfusions performed every year. Blood transfusions are often necessary due to, traumatic injuries, surgeries, or chronic illnesses such as anemia, sickle cell disease, hemophilia, and certain cancers.¹ Blood transfusions are an invaluable resource in treating these medical conditions as they supply the body with red blood cells, plasma, platelets, and cryoprecipitate. These blood components respectively provide oxygen, deliver nutrients, and help form clots.² When a patient requires a blood transfusion, healthcare professionals must ensure that the donor blood type is compatible with the patient. This is particularly difficult for patients who have rare blood types, and with recent blood shortages, researching alternatives could mitigate future crises.

RESTORE Clinical Trial

The Recovery and Survival of Stem Cell Originated Red Cells (RESTORE) trial is an ongoing randomized, controlled clinical trial facilitated by the National Health Service Blood and Transplant (NHSBT) in conjunction with the University of Bristol and National Institute for Health and Care Research Cambridge Clinical Facility. RESTORE aims to test the lifespan of lab-grown blood cells in comparison to donated blood cells which are both sourced from the same donor.³ Using the pluripotent stem cells from the donated blood, researchers are able to cultivate them into red blood cells. For about 3 weeks, they are cultured in 24 liters of nutritional broth which will produce just enough for 1 miniature transfusion. At a minimum, 10 study volunteers will be injected with a 10 mL blood transfusion of lab-grown red blood cells, which will then be compared to a regular blood transfusion of the same cell quantity. Volunteers will receive the 2 transfusions at least 4 months apart. After 6 months of the first transfusion, blood samples will be collected. The red blood cells have tracers attached which will allow the researchers to detect the longevity of the red blood cells.³

Importance and Utility

The RESTORE Clinical Trial is the first lab-grown blood transfusion in humans. Currently, those with chronic hematological conditions depend on maintenance blood transfusions which can come with complications such as iron overload, infections, or injection site reactions.^2,3 With donated blood, the transfusion would contain both old and new red blood cells. In contrast, lab-grown blood transfusions only carry new red blood cells due to being newly cultured from stem cells which hypothetically increases the cells’ longevity in systemic circulation. The longer systemic circulation of red blood cells gives transfusions an extended duration of action, resulting in less frequent administration and therefore, fewer complications.⁴

Additionally, hemolytic transfusion reactions can occur when immune cells attack donated red blood cells. The pathogenesis of this complication is due to the adaptive immune system. The adaptive immune system consists of immune cells that differentiate pathogens from human cells through the identification of endogenous and exogenous antigens.⁵ In hemolytic transfusion reactions, donated red blood cells are subject to this mechanism due to the presence of foreign antigens. These antigens activate the adaptive immune system, leading to the production of antibodies and opsonization of red blood cells for phagocytosis, rendering the treatment ineffective.⁶ With greater research, lab-grown red blood cells can be modified to be without antigens, potentially resolving hemolytic transfusion reactions. Those with rare blood types may also receive manufactured blood tailored to their blood type.³ The Ro subtype is rare and often in demand for those with sickle cell disease.⁷ Demand for the Ro subtype is increasing by 10-15% every year, outpacing the supply of the 2% of donors who have this subtype.⁸ In line with hemolytic transfusion reactions, personalized rare blood transfusions can be produced with the appropriate expression of antigens to be compatible with patients and alleviate the lack of supply of rare blood types.

Unfortunately, in-demand blood types have essentially been extended from rare blood types to every blood type. The American Red Cross declared a blood shortage stating that supply was at a critically low level.⁹ Low-income countries are especially susceptible, often only receiving a seventh of the amount of donations that high-income countries do.¹⁰ The urgent need for blood cannot be understated. The RESTORE Clinical Trial is an innovative stepping stone for hematological and personalized therapy that, with further developments, holds promise as a viable alternative for patients.

References

1. Why patients receive blood transfusions. American Red Cross. https://www.redcrossblood.org/donate-blood/blood-donation-process/what-happens-to-donated-blood/blood-transfusions/reasons-transfusions.html
2. Blood transfusion. Cleveland Clinic. Published October 29, 2020. https://my.clevelandclinic.org/health/treatments/14755-blood-transfusion
3. Kale SSS, Kode R, Kuchana SK, Kutikuppala LVS. Breakthrough in the scientific world: Lab-grown red blood cells used in transfusions. Asian J Transfus Sci. 2023;17(1):143-144. doi:10.4103/ajts.ajts_148_22
4. Lab grown blood given to people in world-first clinical trial. Cambridge University Hospitals. Published November 7, 2022. https://www.cuh.nhs.uk/news/lab-grown-blood-given-to-people-in-world-first-clinical-trial/
5. Alberts B, Johnson A, Lewis J, et al. The adaptive immune system. In: Molecular Biology of the Cell. 4th ed. Garland Science; 2002. https://www.ncbi.nlm.nih.gov/books/NBK21070/
6. Strobel E. Hemolytic Transfusion Reactions. Transfus Med Hemother. 2008;35(5):346-353. doi:10.1159/000154811
7. Demand for different blood types. NHS Blood Donation. www.blood.co.uk/why-give-blood/demand-for-different-blood-types
8. Rare blood types. NHS Blood Donation. www.blood.co.uk/why-give-blood/demand-for-different-blood-types/rare-blood-types
9. Blood shortage continues, please give blood now. Press release. American Red Cross. Published September 20, 2023. www.redcross.org/about-us/news-and-events/press-release/2023/red-cross-announces-national-blood-shortage.html
10. Blood safety. World Health Organization Regional Office for Africa. www.afro.who.int/health-topics/blood-safety‌

Published by Rho Chi Post