In a preclinical study published in Nature Immunology, researchers at Weill Cornell Medicine uncovered how the protein FLI-1 plays a crucial role in activating blood stem cells, enabling them to regenerate more effectively. This discovery could improve the outcomes of therapies that rely on stem cell transplants and gene therapies, such as treatments for certain cancers and blood disorders.
Stem cells, which typically remain in a quiescent (inactive) state, are capable of activating and rapidly multiplying to regenerate tissues in response to injury or need. In the study, scientists identified FLI-1 as a key regulator of this activation process in blood stem cells. When introduced transiently into these cells via modified mRNA, FLI-1 prompts them to expand rapidly and increases their potential for successful transplantation into a new host.
“We have shown that by temporarily activating FLI-1 in quiescent blood stem cells, we can improve their expansion and regenerative ability, potentially enhancing outcomes for patients requiring marrow transplants or gene therapies,” said Dr. Shahin Rafii, the senior author of the study and a professor at Weill Cornell Medicine.
This method could be particularly valuable in cases where the donor’s blood stem cell supply is limited, such as in patients who have undergone chemotherapy or radiation, which can impair the function of stem cells. Additionally, gene therapies that require the harvesting, modification, and expansion of blood stem cells, such as treatments for blood disorders like beta-thalassemia, could benefit from this technique.
Through detailed single-cell profiling, the researchers were able to pinpoint how FLI-1 interacts with the vascular niche—the microenvironment that supports stem cell function in the bone marrow. Their findings suggest that FLI-1 facilitates a critical connection between blood stem cells and the endothelial cells of blood vessels, helping the stem cells enter an activated state.
Importantly, the researchers found that the method does not pose a cancer risk, as they were able to regulate the activation of FLI-1 in a controlled manner, using an approach akin to that of mRNA vaccines.
