Blood stem cells offer promise for a variety of immune and blood related disorders such as sickle cell disease and leukemia. Like other stem cells, blood stem cells have the ability to generate additional blood stem cells in a process called self-renewal. Additionally, they are able to generate blood cells in a process called differentiation. These newly generated blood cells have the potential to be utilized for transplantations and gene therapies.

However, two limitations have hindered the progress made in this field. One problem relates to the amount of blood stem cells needed to make a potential transplantation or gene therapy viable. Unfortunately, it has been challenging to isolate and grow blood stem cells in large quantity needed for these approaches. A part of this reason relates to getting the blood stem cells to self-renew rather than differentiate.

The second problem involves the existing blood stem cells in the patient’s body prior to transplantation. In order for the procedure to work, the patient’s own blood stem cells must be eliminated to make space for the transplanted blood stem cells. This is done through a process known as conditioning, which typically involves chemotherapy and/or radiation. Unfortunately, chemotherapy and radiation can cause life-threatening side effects due to its toxicity, particularly in pediatric patients, such as growth retardation, infertility and secondary cancer in later life. Very sick or elderly patients are unable to tolerate this conditioning process, making them ineligible for transplants.

A CIRM funded study by a team at Stanford and the University of Tokyo has unlocked the code related to the generation of blood stem cells.

The collaborative team was able to modify the components used to grow blood stem cells. By making these modifications, which effects the growth and physical conditions of blood stem cells, the researchers have shown for the first time that it’s possible to get blood stem cells from mice to renew themselves hundreds or even thousands of times within a period of just 28 days. 

Furthermore, the team showed that when they transplanted the newly grown cells into mice that had not undergone conditioning, the donor cells had engrafted and remained functional.

The team also found that gene editing technology such as CRISPR could be used while growing an adequate supply of blood stem cells for transplantation. This opens the possibility of obtaining a patient’s own blood stem cells, correcting the problematic gene, and reintroducing these back to the patient.

The complete study was published in Nature.

In a news release, Dr. Hiromitsu Nakauchi, a senior author of the study, is quoted as saying,

“For 50 years, researchers from laboratories around the world have been seeking ways to grow these cells to large numbers. Now we’ve identified a set of conditions that allows these cells to expand in number as much as 900-fold in just one month. We believe this approach could transform how [blood] stem cell transplants and gene therapy are performed in humans.”