Advances in Fetal Repair of Spina Bifida Integrating Prenatal Surgery, Stem Cells, and Biomaterials

Major Points and Findings:

This narrative review from the University of Pavia, Italy, covers how spina bifida arises, how it is diagnosed before birth, how fetal surgery has developed, and where stem cells and engineered patches fit in. The authors do not describe a search strategy or grade the quality of the studies they cite, so it cannot be read as a systematic review. With 55 references it is a selective overview.

The review is open about how little stem cells can currently offer in spina bifida. Almost all of the evidence is from rats and sheep. The authors describe clinical readiness as “distant”, and they set out in a table the specific weakness of each experimental approach. Nearly all of the review concerns treatment before birth, and it says very little about cell therapy for children already living with the condition.

Aim:

To give an integrated overview of the embryology, diagnosis and prenatal treatment of spina bifida, with emphasis on fetal surgery and on emerging regenerative approaches, namely mesenchymal stem cells (MSCs), biomaterial scaffolds and cell-derived products such as exosomes.

Methods:

The paper is a narrative literature review with no stated databases, search dates or inclusion criteria. The experimental cell and scaffold studies are collected in one table that lists, for each, the cell source, the scaffold, the type of surgery, the animal model, the effect and the limitation. The authors, from drug sciences and surgical departments, develop their own scaffold, which the review also describes. They declare no conflicts of interest, and state that an AI tool was used to create the figures but not the text.

Results:

Pooled prevalence of spina bifida is 33.9 per 100,000 live births in regions with mandatory folic acid fortification and 48.4 per 100,000 where fortification is voluntary or absent, with some estimates from Asia and Africa exceeding 80 to 200 per 100,000. Newborn mortality in myelomeningocele remains about 10%, and only about half of survivors achieve functional independence as adults.

The authors use the “two-hit” model of the condition. The first hit is failure of the neural tube to close between days 22 and 28 after conception. The second is months of damage to the exposed cord from amniotic fluid, inflammation and mechanical trauma. Both fetal surgery and cell therapy are aimed at the second hit.

Fetal surgery: In the MOMS trial, open repair at 19 to 26 weeks lowered shunt placement (44% against 84% at 12 months in the expanded analysis of 183 patients, with shunt revisions 15.4% against 40.2%) and raised independent walking at 30 months (44.8% against 23.9%). The risks fall on the mother. They include preterm rupture of membranes, preterm delivery, uterine scar separation, and caesarean delivery for this and all later pregnancies. Keyhole (fetoscopic) repair, with more than 300 cases in an international consortium, avoids uterine scar separation and allows vaginal birth in up to a third of cases, but takes longer and has membrane rupture rates of about 50% to 60% in several series. No large randomised trial has compared the keyhole and open techniques.

Stem cell approaches:

• Transamniotic stem cell therapy (TRASCET) uses MSCs from amniotic fluid or placenta, injected into the amniotic fluid under ultrasound with no surgery. In rodents it produced partial or complete skin-like coverage of the defect in 46% (amniotic fluid MSCs) and 47% (placental MSCs). The review’s table lists rodent-only data, poor cell tracking and no significant functional improvement as its limits. It has not been validated in large animals and lacks long-term safety data.
• Placental MSCs on a matrix patch improved motor neuron survival and movement in lambs. This approach is now in the first human fetal trial (CuRe, NCT04652908).
• Umbilical cord MSCs in a fibrin patch gave better motor function, higher neuron density, less scarring and preserved urinary continence in lambs, with no tumours and no spread of cells. The review also records the weaknesses, which were small and variable samples, non-significant locomotor scores, surgical variability and very early assessment.
• Bone marrow MSCs on chitosan-gelatin scaffolds in fetal rats reduced the defect and nearly closed the skin, but cell survival was low.
• Exosomes from placental MSCs protected nerve cells in a dish through a protein called galectin-1. Low yield, variable composition and the absence of agreed potency tests are listed as obstacles.
• Treatment of children after birth receives one sentence in the review. Intravenous Wharton’s jelly MSCs in paediatric patients were well tolerated and “correlated with” improvements in bladder and bowel control, cognition and quality of life, “although randomized trials are still needed”.

Mechanism: Across studies the benefit is attributed to substances the cells secrete (growth factors, anti-inflammatory and anti-scarring signals). The cells are not thought to become part of the spinal cord. The authors report that placental MSCs were neuroprotective “without engraftment”.

Scaffolds: Gelatin sponges, growth factor-loaded collagen, umbilical cord membrane, fibrin patches, commercial dural substitutes and aligned nanofibres have all been tried in animals. Recurring problems are scaffold detachment, contraction, mechanical weakness and absent long-term functional data. The authors’ own heat-responsive shape-memory scaffold, designed to unroll over the defect at body temperature, has so far been tested only in the laboratory with one material composition.

Conclusions:

The authors conclude that fetal repair, open or keyhole, remains “primarily protective rather than truly regenerative”. They consider MSC-based and scaffold-based additions biologically plausible and encouraging in animals. Clinical use, in their view, depends on work not yet done. This includes validation in large animals, standardised functional endpoints, long-term safety data on tumour formation and cell migration, and manufacturing to medicinal product standards with validated potency tests. For future trials they recommend a minimal common outcome set consisting of lesion closure and dural integrity at birth, standard motor assessments, uniform shunt criteria, bladder and bowel continence, and age-appropriate cognitive testing.

The authors also raise ethical concerns. Fetal intervention exposes the mother to risk with no direct benefit to her, and expertise is concentrated in a few centres, which limits fair access.

Background Information:

Some points should be kept in mind when reading this review.

• It was published in January 2026, a few weeks before the first CuRe trial results appeared in The Lancet, so it could only describe that trial as ongoing. Its wording that early clinical use of placental MSCs has “reported encouraging functional signals” goes further than the published phase 1 results, which reported safety at birth in six babies and no functional outcomes.
• Its table names the CuRe patch material as Durepair. The trial’s own publication names the Cook Biodesign Dural Graft. Our summary of that study follows the trial publication.
• The table repeats an identical list of limitations for two different sheep studies, which looks like an editing slip. The review does not discuss the 2023 Vietnamese trial of intrathecal bone marrow cells in children with spina bifida.

On postnatal cell therapy, the review shows that the main scientific effort is going into protecting the cord before birth, when damage is still accumulating. For children and adults whose cord damage is established, the evidence it cites is thin. It consists of small, uncontrolled studies that the authors say still need randomised confirmation.