Why do fetuses reject stem cell implants? Researchers have puzzled over this for a decade. A new mouse study suggests that the mother's immune system is to blame – and as it turns out, her stem cells are also the solution.
As early as the first trimester of pregnancy, doctors can diagnose certain genetic diseases – which they’ve hoped to treat with fetal stem cell transplants because immature immune systems should better tolerate foreign substances.
Implanted cells should replenish the fetus’s supply of healthy blood-forming cells, but these transplantations haven’t been very successful.
According to new research, it’s the mother’s immune response that prevents the fetus from accepting transplanted blood stem cells. And the solution? Transplanting cells harvested from the mother herself.
Researchers from the University of California at San Francisco figured that out by taking a close look at the blood cells of mouse embryos (pictured).
1. First, they found that up to 10% of the fetus’s blood cells came from the mother – an unexpectedly large proportion. It made them think that it’s the maternal, rather than fetal, immune response that “poses the real barrier to effective stem cell transplantation,” says study author Tippi MacKenzie.
2. Then they conducted the transplant with blood from unmatched mice donors. They watched as the mother’s immune cells traveled into the fetus and rejected the transplant. “The surprising finding in our study is that the mother’s immune system is to blame,” coauthor Qizhi Tang explains.
3. Next, they removed immune cells from the mother before the transplant, and got a nearly 100% success rate.
4. So they figured out the solution and transplanted fetal mice with blood stem cells harvested from the mother – which “makes sense because the mother and her developing fetus are prewired to tolerate each other,” adds coauthor Amar Nijagal.
“This research is really exciting because it offers us a straightforward, elegant solution that makes fetal stem cell transplantation a reachable goal,” MacKenzie says. “We now, for the first time, have a viable strategy for treating congenital stem cell disorders before birth.”
The team next hopes to confirm the study in humans. This finding was published in the Journal of Clinical Investigation online last week.
Image: Journal of Clinical Investigation via MIT Technology Review