New Strategy Shows Potential in Expanding Blood Stem Cells

The Wisconsin Alumni Research Foundation recently secured a provisional patent to protect a new strategy to increase the number of blood stem cells.

According to a new study published early online in Stem Cell Reports, Emery Bresnick, a professor of cell and regenerative biology and the director of the UW-Madison Blood Research Program at the UW School of Medicine and Public Health, has identified a genetic circuit that inhibits blood stem cell production.

But in studying the circuit, he’s also identified a compound that can shut down the circuit’s negative feedback loop and promote blood stem cell and progenitor cell production.

If the technology can be applied to cord blood and transferred to the clinical setting, it could one day enable a hospital-based procedure to take a cord-blood sample and multiply its valuable stem and progenitor cells before infusion.

Cord blood can be collected and stored at cord-blood bank facilities until needed. Most cord-blood transplants are coordinated through the National Marrow Donor Program. Once matched, the blood is prepared and delivered through an IV to its recipient. The blood-forming cells then circulate through the body and settle in the bone marrow.

More than 50,000 stem cell transplants occur annually, 2,000 of which are cord blood transplants.

Patients seeking bone-marrow transplant must match all six HLA types with a donor for a successful match; cord blood matching requires only matching four of the 6 HLAs between donor and patient.

Cord blood has been used to treat many different blood disorders, immunodeficiencies, cancers and other disorders. And while delivery is deceptively simple, the several months after a transplant are critical to the patient’s recovery as physicians monitor the patient’s health and fight infections.

But while it’s becoming more common for adult patients to receive multiple cords to help ensure enough stem cells are transfused, the use of multiple cords may be associated with increased graft-versus-host disease, where the newly introduced cells treat the host as foreign. Thus, effective strategies to increase the number of stem cells from a single cord will have multiple benefits.

In a jump from basic research to potential clinical applications, the Bresnick lab has long been studying a gene that controls many different blood-producing functions. During their study of Gata2 (Gata2 the gene, and GATA-2 the protein produced by the gene), Cell and Molecular Biology graduate student Xin Gao and undergraduate researcher Sophie Wu, in collaboration with other members of the Bresnick group, uncovered GATA-2-regulated genes that mediate the generation, survival and function of blood stem cells and progenitors.

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