Prenatal stem cell transplant is emerging as an alternative to bone marrow transplant for hereditary conditions such as sickle cell disease and thalassemia. But first, experts must find a way to beat a developing infant’s natural killer (NK) cells.

That’s the mission for Aimen Shaaban, MD, a fetal surgeon who joined Cincinnati Children’s last year to become Director of the Center for Fetal Cellular and Molecular Therapy. He is using a five-year, $1.9 million grant from the National Heart, Lung & Blood Institute to learn more about when NK cells become active during fetal development.

Chance to cure before symptoms begin

The potential advantage of fetal stem cell therapy comes from providing treatment before the immune system develops.

“We have the technology to detect specific genetic diseases as early as six or seven weeks’ gestation, which gives us an opportunity to provide therapy while the fetus still has no immune system. This could cure certain diseases before symptoms ever begin,” Shaaban says.

While some successes in human fetal therapy have been reported, clinicians also have reported unexpected, repeated failures. Shaaban and colleagues may have found a way to improve the odds.

NK cells may determine therapy timing

Preliminary studies in mice reveal that knocking down the function of NK cells – an early-developing part of the immune system -- gives transplanted stem cells the time they need to establish themselves. After a few weeks, when NK-suppressing drugs are stopped, the transplanted cells continue to function as intended.

Shaaban’s team is expanding on these findings by determining more precisely how and when NK cells become active during fetal development. Their findings could help set new protocols for fetal therapy ranging from the timing and volume of donor cell doses to determining the need for booster transplants.

Prior to joining Cincinnati Children’s, Shaaban directed fetal cellular therapy labs at the University of Iowa and the University of Wisconsin.