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