Chou ST et al. present customized induced pluripotent stem cell-derived red cell reagents for the treatment of patients with sickle cell disease.
Researchers are announcing one of the first applications of induced pluripotent stem cells (iPSCs) poised to improve day-to-day clinical care of people with SCD. They report using the gene-editing platform CRISPR/Cas9 to engineer a panel of stem cell-derived red blood cells to guide rapid identification of antibodies common among people with SCD to allow for quicker, more efficient matching of blood for transfusions.
People with SCD frequently require blood transfusions, but the formation of uncommon antibodies in their blood often makes it challenging to find donor blood that is safe to use for these patients. By helping patients with SCD quickly find matched donor blood, the new screening panel represents a groundbreaking achievement in the use of stem cells and genetic engineering. “It has been more than 10 years since iPSCs have been available, but we have yet to see applications for blood diseases that improve how we care for our patients,” said lead study author Stella T. Chou, MD, assistant professor of pediatrics at Children’s Hospital of Philadelphia (CHOP). “Using this panel, we would be able to more quickly identify what antibodies the patient has made, informing us what kind of blood we have to give them. It means we’ll be able to improve their ability to be transfused safely and reduce delays in their care.”
The work centers around a group of antibodies associated with the Rh blood group system. Individuals with SCD often have variations or mutations in the RH gene, which alters the Rh proteins on their red cells. Despite patients receiving blood that is “Rh-matched” by standard blood bank tests for Rh, having these variant proteins increases their risk of forming Rh antibodies with transfusions. If a person with Rh antibodies receives a blood transfusion that is not matched correctly, the recipient’s immune system treats the donated blood as foreign and destroys the transfused red cells.
While RH variants occur in only one to two percent of the general population, they are much more common in people with SCD. Dr. Chou said they are found in more than half of the children with SCD treated at CHOP. This is largely because of the increased prevalence of RH variants in people of African descent, who make up the majority of people living with SCD.
For patients dependent upon donor blood with perfectly matched Rh, transfusable blood is often hard to come by. Routinely RH genotyping all donated blood to better match eventual patients is extremely costly, and testing blood in the donor pool to find an appropriate candidate can take days. To address these problems, the researchers used iPSCs, which can become any cell in the body, to create an array of blood cells with rare red cell antigen combinations that could be used to quickly test for Rh antibodies. To reflect clinically important Rh variations, the researchers used blood from donors with rare RH variants and also genetically altered some iPSCs using CRISPR/Cas9 to create blood cells with specific combinations of antigens. With further refinement of this technique, the researchers from CHOP and New York Blood Center hope to develop a simple, cost-effective screening tool that could be used at local blood banks across the country to help doctors quickly find Rh-matched blood for people with SCD.
This study was supported by the National Institutes of Health/National Heart Lung and Blood Institute.
Stella T. Chou, MD, The Children’s Hospital of Philadelphia, will present this study during an oral presentation on Sunday, December 10, at 2:00 p.m. EST in Hall C2 of the Georgia World Congress Center.
ASH Annual Meeting 2017, abstract #3