Could a simple injection fix spina bifida before birth?

Mesenchymal stem cells derived from amniotic fluid (FAUZA LAB / BOSTON CHILDREN’S HOSPITAL)

Ed. note: This is an update of a post that originally appeared in 2014.

The neural tube is supposed to close during the first month of prenatal development, forming the spinal cord and the brain. In children with spina bifida, it doesn’t close completely, leaving the nerves of the spinal cord exposed and subject to damage. The most common and serious form of spina bifida, myelomeningocele, sets a child up for lifelong disability, causing complications such as hydrocephalus, leg paralysis, and loss of bladder and bowel control.

A growing body of research from Boston Children’s Hospital, though still in animal models, suggests that spina bifida could be repaired at least partially early in pregnancy, through intrauterine injections of a baby’s own cells.

Currently, the standard procedure is to operate on infants with spina bifida soon after delivery. Some infants undergo fetal surgery to cover over the malformation before birth, which can minimize damage to the exposed spinal cord, caused by fetal movement or from amniotic fluid itself. But fetal surgery cannot be done safely until the 19th to 25th week of pregnancy, when much of the nerve damage has already occurred. It also carries some risk, may trigger a preterm delivery and not every mother-infant pair is eligible.

Transamniotic stem cell therapy

Prenatal cell therapy could avoid the need for invasive surgery for spina bifida. (ILLUSTRATION: WIKIMEDIA)

That’s where surgeon and tissue engineering pioneer Dario Fauza, MD, PhD, comes in. He has conducted more than a decade of testing in a series of animal models showing that amniotic fluid, commonly drawn from expectant mothers by amniocentesis, particularly when the developing baby has an anomaly such as spina bifida, contains a unique population of mesenchymal stem cells. Fauza and colleagues have shown that these cells, present throughout pregnancy, naturally repair fetal injuries in utero. And they can be expanded rapidly in a laboratory dish.

“Even though I am a surgeon, the idea of harnessing natural healing non-surgically is very appealing,” says Fauza.

In 2014, Fauza, with his research fellow Beatrice Dionigi, MD, and other colleagues, reported that these stem cells, expanded in the lab and injected back into the womb in large numbers, caused skin to grow over the spinal cord in a rat model, sometimes completely covering the defect.

Harnessing natural repair mechanisms

This method — which Fauza calls Transamniotic Stem Cell Therapy, or TRASCET — will of course require more testing before it can be tried in humans, but it has the potential to be a safe and very practical option to prevent more damage to the spinal cord.

Dario Fauza, MD, PhD“The problem with surgical closure is that you can only do it relatively late in the pregnancy,” says Fauza. “We found out that you may not need to operate: If you inject cells in large enough amounts, they will trigger coverage of the defect, at least in this animal model. And you can potentially inject these cells very early in pregnancy and offer the treatment to many more patients.”

More recent work has extended the 2014 finding to a large animal model. The team has also shown that fetal cells from the placenta have the same properties as those derived from amniotic fluid. This could enable intervention even earlier in pregnancy: While prenatal amniocentesis is typically done at 16 weeks, placental cells can be obtained during chorionic villus sampling (CVS) at 12-13 weeks of pregnancy.

Minimizing Chiari II malformation, bone marrow homing

Fauza’s team also found, in a rodent model, that TRASCET can minimize the Chiari II malformation that often accompanies spina bifida. This malformation, a result of leaking fluid from the brain and spinal cord, displaces the brainstem and cerebellum. This, in turn, sometimes causes fluid to accumulate inside the brain, leading to hydrocephalus.

We ultimately want to get permission from the FDA to try this in a clinical trial.

“We measured cerebellum and brainstem displacements and found that Chiari II was minimized, secondary to coverage of the spina bifida defect,” says Fauza.

Earlier this year, the team reported a surprising discovery: When they labeled the injected cells, they found the cells didn’t go directly to the spinal defect, as expected. Instead, they homed to the bone marrow — and from there orchestrated the healing process.

“This was an important insight,” says Fauza. “We don’t quite know how, but what seems to be happening is these cells are turbo-charging the bone marrow of the fetus to contribute to a regenerative process that leads to coverage of the defect.”

From the lab to the clinic

Over the years, Fauza has repeatedly put amniotic mesenchymal stem cells through their paces, demonstrating the ability to expand them in the lab in conformance with FDA Good Manufacturing Practice (GMP). His lab has also used these mesenchymal stem cells in animal models of tracheal reconstruction, congenital diaphragmatic hernia and gastroschisis.

“Our next hurdle is fine-tuning the technique for spina bifida and demonstrating functional benefits in the mid- to long-term,” says Fauza. “We do know that every time you cover the defect earlier, the child does better clinically. We ultimately want to get permission from the FDA to try this in a clinical trial.”

For more on care of spina bifida at Boston Children’s, visit the Spina Bifida and Spinal Cord Conditions Center or follow the Center on Facebook.