Stem cell patch reverses brain damage in fetuses with spina bifida

A patch made of stem cells from donor placentas has been used to treat fetuses in the womb with a severe form of spina bifida as part of a world-first trial. The novel approach seems to have reversed a brain complication associated with the congenital condition at least as effectively as the go-to treatment, but is expected to enable more children to walk over the long term.

The mother of one of the babies, who is now 4 years old, says she expected that her son Toby would require a wheelchair when he was diagnosed with the condition in the womb. “But Toby is healthy [and] has hit all of his milestones – he’s walking, running and jumping – and has no problems with bladder control, which is rare for people with the condition,” she says.

Spina bifida – which affects about 1 in every 2800 births in the US every year – occurs when a baby’s spine and spinal cord do not fully develop in the womb. In the most severe form of the condition, called myelomeningocele, the spinal cord and its surrounding tissue protrude out of a gap in the vertebrae, which often impairs mobility and bowel and bladder control. The cause of spina bifida is unknown, but folic acid deficiency during pregnancy raises the risk.

One of the standard treatments involves surgery in the womb that tucks the spinal cord and the surrounding tissue back into the vertebrae, before sewing up the skin to form a tight seal. “But many children still end up unable to walk and there’s [usually] no improvement in bowel or bladder control,” says Diana Farmer at the University of California, Davis.

This led Farmer and her colleagues to wonder if the addition of stem cells could help by promoting the growth and repair of spinal tissue. To find out, they recruited six pregnant women carrying fetuses with myelomeningocele.

By about 24 weeks’ gestation, all the fetuses had developed a common complication called hindbrain herniation, where too much fluid builds up in the skull, pushing the bottom of the brain, the cerebellum, through a hole at the skull’s base. The standard surgery often helps to reverse hindbrain herniation, but many children still have complications.

In the latest trial, all the fetuses underwent the standard surgery but also received a patch, measuring a few centimetres long, that contained stem cells derived from donated placentas that were embedded in a matrix of sticky proteins. Surgeons placed this patch on the spine before the skin was sewn around it. “The cells secrete their magic stem cell juice,” says Farmer.

At birth, the surgery site had healed well in all of the babies, with no signs of abnormal cell growth. “A key worry was that adding stem cells in a fetus would make the cells grow like crazy, but we didn’t see that,” says Farmer. MRI scans of their brains also showed that the treatment completely reversed hindbrain herniation.

“My personal opinion is that this will improve long-term outcomes compared to the standard approach [based on evidence from animal studies],” says Panicos Shangaris at King’s College London.

The researchers hope to assess this in a trial where 35 fetuses with myelomeningocele will receive the stem-cell patch, and their outcomes will be compared against a previous study that used the conventional surgery, says Farmer.

But Shangaris says that a better comparison, which is more likely to lead to the treatment being approved, would be to compare the two approaches in a head-to-head trial that assesses their safety and efficacy on fetuses who were randomly assigned to each intervention.