Stem Cells Applied to Fetal Spines During Surgery Are Safe in Phase 1 Spina Bifida Trial

Spina bifida is diagnosed before birth in many cases, and for the most severe form - myelomeningocele, in which part of the spinal cord protrudes through an opening in the spine - fetal surgery has become a standard option. Operating on a fetus in the womb to close the spinal opening reduces some complications compared to postnatal repair. But it does not prevent all neurological damage. Paralysis, difficulty walking, and lifelong problems with bladder and bowel control remain common outcomes even after successful fetal closure.

The question researchers at several centers have been pursuing is whether adding a biological component to the surgical repair - specifically, cells with the ability to reduce inflammation and support nerve tissue recovery - could improve outcomes beyond what structural closure alone achieves. A phase 1 clinical trial published in The Lancet provides the first human evidence that this approach, at least in its safety profile, is feasible.

Six Pregnancies, One Additional Step

Six pregnant women carrying fetuses diagnosed with myelomeningocele underwent the trial between July 2021 and December 2022. Each received standard fetal surgery to close the spinal opening, with one addition: surgeons applied placenta-derived mesenchymal stem cells - known as PMSCs - directly onto the exposed spinal cord during the procedure.

PMSCs were chosen for specific reasons. They are accessible from the placenta without invasive procedures, they can reduce inflammation, they promote tissue healing, and they have a capacity to protect nerve cells - properties that made them plausible candidates for limiting secondary neurological injury after spinal closure.

All six babies were born with their spinal repairs intact. None showed signs of infection, abnormal tissue growth, or tumor formation - the safety signals most closely watched in any first-in-human stem cell study. Post-birth MRI scans confirmed that hindbrain herniation, a brain abnormality consistently associated with myelomeningocele in which part of the cerebellum is pushed downward through the base of the skull, was reversed in every case. No serious adverse effects attributable to the stem cell treatment were observed during the trial or through follow-up care.

What Phase 1 Can and Cannot Establish

The purpose of a phase 1 trial is safety, not efficacy. With six participants, this study has no statistical power to determine whether children who received stem cells alongside surgery have better motor function, bladder control, or quality of life than children who received surgery alone. That question requires the larger controlled trials that are now underway.

The trial also does not yet have the long-term follow-up needed to be certain that no delayed adverse effects will emerge. The children will be monitored with regular assessments until they turn six, providing a structured window for detecting any late problems with the stem cell treatment. That monitoring will continue as the next phase of research proceeds.

The specific surgical technique for applying the cells, and the protocols for preparing and handling PMSCs, will also need refinement as the research scales. Regulatory agencies will work closely with the research team throughout this process.

The Significance of the First-in-Human Data

The reversal of hindbrain herniation in all six cases is a noteworthy finding. This particular brain abnormality causes a range of problems including hydrocephalus - fluid buildup in the brain - and when it resolves after fetal spinal closure, it typically reflects successful repair. Its consistent reversal across all six cases is consistent with what is seen after standard fetal surgery alone, confirming that adding stem cells did not disrupt the expected benefits of the surgical repair itself.

The researchers frame these results as establishing safety and feasibility as prerequisites for the efficacy studies that will determine whether this approach actually improves neurological outcomes. The fact that it is the first time live stem cells have been used on a fetus's damaged spine makes the safety data alone a meaningful step, regardless of what the efficacy studies ultimately show.