Synthesising Blood Stem Cells for the First Time
Two new studies in Nature (1 and 2) have proven that it may be possible in the future to treat blood disorders by using a patient’s own endothelial cells to create haematopoietic stem cells. This is the first time that scientists have been able to grow blood stem cells in the lab.
Haematopoietic stem cells are capable of differentiating into a multitude of different blood cells, including ones that play important roles in the human immune system, such as B and T cells and myeloid cells. As a result, they can be used to treat a number of blood and immune system disorders. These transplants usually take the form of bone marrow, the tissue type that is rich in blood stem cells but there are problems with this approach.
Most importantly, the demand for bone marrow greatly exceeds the supply, meaning that patients frequently have to wait for transplants to become available. There are also problems associated with finding a match for a patient; because of the implications to the immune system, it is vital that a donor shares significant biological similarities to the patient.
One way of avoiding both of these problems might be to take cells from the patient themselves, and then convert them into haematopoietic stem cells chemically. This process generally involves stepwise exposure to morphogens or enforced expression of master transcription factors, thereby changing the cellular state. Doing this in a laboratory, however, has proven difficult in previous studies.
Now two papers have managed to synthesise haematopoietic stem and progenitor cells in a lab using these techniques.
The first paper was released by researchers at Weill Cornell Medical College in New York. The team, led by Shahin Rafil, M.D., were able to reprogram adult mouse endothelial cells into haematopoietic stem cells using transient expression of four genes responsible for transcription factors (Fosb, Gfi1, Runx1, and Spi1). Their method also used vascular-niche-derived angiocrine factors.
The second paper came from researchers at Boston Children’s Hospital in Massachusetts. Led by George Daley, Ph.D., M.D., this team chose to work with human pluripotent stem cells using mice as hosts. In this study, both morphongens and transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, and, like the other group, Runx1 and Spi1) were used to convert the cells, yielding both haematopoietic stem and progenitor cells within primary and secondary mouse recipients.
Both studies were relying on mouse models but they offer important insight into how we might be able to synthesise blood stem cells in patients in the future.
“Our study suggests that we are tantalizingly close to realizing the potential of derivation of HSC-like cells from PSCs,” wrote the authors of the second paper. “Such cells, when derived from patients with genetic blood disorders, offer considerable promise for modelling human blood disease, for humanizing mice for research applications, and for testing the capacity of gene therapy vectors or pharmacological agents to restore haematopoietic function. Our ultimate goal remains the derivation of bona fide transgene-free HSCs for applications in research and therapy.”