Fetal Myelomeningocele Repair: A Narrative Review of the Historical Perspective, Emerging Regenerative Therapies, and Future Directions

Major Points and Findings:

This is a short narrative review written by the University of California, Davis team led by Dr. Diana Farmer, the group running the CuRe trial of placenta-derived stem cells applied during fetal surgery for myelomeningocele (MMC), the most severe form of spina bifida. It explains why surgeons began closing the defect before birth, summarises what the MOMS trial showed, and then describes the patches, engineered tissues and stem cell approaches being tested to improve on surgery alone. It reports no new data of its own.

The review is a useful overview of where the field stands in 2026, but readers should know what kind of paper it is. It is not a systematic review, the authors chose which studies to discuss, and they are describing their own trial among others. Its main message is cautious. Open fetal surgery as done in MOMS is still the best-studied treatment and the benchmark for everything else, and stem cell treatment before birth has so far reached only early safety testing in six babies.

Aim:

To give an overview of the rationale and history of prenatal MMC repair, describe regenerative strategies (biomaterials, tissue engineering and stem cells) aimed at improving on it, and outline directions for future work.

Methods:

A narrative review. The paper does not describe a literature search strategy, inclusion criteria or any quality assessment of the studies it discusses, and it cites 66 references. It is organised into sections on the rationale for fetal surgery, the MOMS trial, the reasons for adding regenerative therapy, tissue engineering and biomaterials, cellular therapies, and future directions.

Results:

Background figures: Spina bifida occurs in about 1 in 2,875 live births. Before fetal surgery, more than 80% of children repaired after birth needed a shunt for hydrocephalus. Spina bifida care is estimated to cost over two billion dollars a year in US hospital and emergency charges alone. The first fetal MMC repair was performed by Dr. Joseph Bruner at Vanderbilt University in 1997.

Why repair before birth: The authors describe the “two-hit hypothesis”. The spinal cord is first damaged when the neural tube fails to close, and then further injured while it lies exposed in the womb during pregnancy. Covering the defect in fetal sheep reduced spinal cord damage and reversed hindbrain herniation. The authors note that the exact timing and reversibility of this second injury are still being studied.

The MOMS trial: The review describes MOMS as the multicenter randomized controlled trial that set the standard of care for carefully selected patients.

• Shunt placement was needed in 40% of babies repaired before birth and 82% of those repaired after birth.
• Hindbrain herniation reversed in 96% versus 64%.
• At 30 months, 42% of the prenatal group walked independently compared with 21% after postnatal repair, and 32% versus 12% functioned two or more levels better than expected from their lesion.
• There were also fewer shunt revisions, and the benefits persisted to school age, with families reporting lower family impact and higher quality-of-life scores.
• The costs to mother and baby included premature rupture of the membranes and preterm birth (mean gestational age at delivery 34.1 weeks), thinning or rupture of the uterine scar, and the need for caesarean delivery in all future pregnancies.

What surgery leaves unsolved: More than half of the children in MOMS still could not walk independently, and most continue to have motor, bladder and bowel problems. Spinal cord tethering and inclusion cysts can occur after both prenatal and postnatal repair and may lead to further surgery.

Patches and biomaterials (mostly for keyhole fetoscopic repair):

• In the CECAM trial, a biocellulose patch was placed on the spinal cord in ten fetuses. There was one fetal death, one newborn death and one baby who needed closure after birth, and delivery came at a mean of 32.4 weeks.
• In the SAFER technique, used in 170 patients, about one-third were born before 32 weeks and 13% had a spinal fluid leak at birth. Of those followed to 30 months, 52% needed a shunt, and 54.2% (32 of 59) walked independently.
• A cryopreserved human umbilical cord patch healed well in animals. The first two human babies were born at 37 weeks with healed wounds, but all four patients in an imaging study showed cord tethering after repair. A phase 3 study is under way without published results.
• None of these materials, or fetoscopic repair in general, has been compared with open fetal surgery in a randomized trial, and long-term outcomes are not well described. The authors write that there is no evidence of better neurological outcomes than with open surgery.

Stem cell approaches:

• A 2021 meta-analysis found 26 animal studies of stem cells for MMC in rats, chicks, rabbits and sheep. Stem cells did not affect survival and caused no major complications in those animals.
• Placenta-derived mesenchymal stromal cells (PMSCs) seeded onto an approved extracellular matrix patch are, in the authors’ words, the first stem cell treatment used in human fetal MMC patients, in the CuRe trial (NCT04652908). In fetal sheep this patch consistently rescued walking compared with the matrix alone, apparently through growth factors such as HGF and BDNF rather than by the cells becoming new nerve tissue. Animal safety studies showed no tumours.
• In the phase 1 part of CuRe, six babies were treated during open fetal surgery and showed a favourable safety and feasibility profile at birth with no product-related adverse events. The trial continues, with motor function at 30 months as the main outcome.
• Umbilical cord mesenchymal stem cells on a fibrin patch improved walking in fetal lambs, and the cells’ DNA was not found in the placenta or other organs. This work was in sheep, and no human fetuses have been treated with it.
• For children after birth, the review mentions a single-centre retrospective study of 28 children given Wharton’s jelly stem cells intravenously. It describes the product as appearing safe, with higher quality-of-life scores and some reported functional improvement, but notes that baseline data were not clearly reported and that comparative studies are needed.
• Other ideas are still at the animal stage only, with no humans treated. These include engineered cartilage, bone and fetal skin for large defects, stem cells injected into the amniotic fluid (TRASCET), and alginate microparticles that settle on the defect.

Conclusions:

The authors conclude that open fetal surgery remains the most thoroughly studied repair and that the MOMS results are the standard against which new therapies must be compared. They suggest that combining fetal surgery with targeted regenerative treatment may further improve function, and they call for standardised fetoscopic techniques, biomaterials designed for minimally invasive delivery, and use of new genetic findings to tailor treatment. Prematurity, membrane rupture, persistent neurological deficits and cord tethering remain unsolved with both open and keyhole approaches. They stress that risks and benefits to mother and baby must stay central to decisions.

As a narrative review, the paper does not weigh the evidence systematically, and the stem cell section relies heavily on the authors’ own sheep studies and the first six CuRe patients. No efficacy data from humans treated with stem cells before birth are yet available, and the review says so.

Background Information:

The authors work at the UC Davis Center for Bioengineering in Medicine, the UC Davis Department of Surgery and the Shriners Children’s Northern California Research Center. Dr. Farmer is first author of the MOMS 30-month outcome report and of the CuRe phase 1 paper, and Dr. Wang is first author of the original sheep study of the placental stem cell patch, so much of the review discusses the authors’ own work. The article PDF contains no funding statement or conflict-of-interest declaration. It is published open access under a CC BY licence.

The review describes MMC as the only non-lethal condition for which fetal surgery is currently performed. The authors also see it as a model for treating other birth defects that worsen in the womb, and they mention an ongoing clinical trial of fetal repair for complicated gastroschisis (NCT05704257).