[PRIUM-Cell: In utero myelomeningocele prenatal repair program using mesenchymal stromal cells]

Lucie Guilbaud; Yoann Athiel; Justine Nasone; Timothée de Saint-Denis; Éléonore Blondiaux; Hina Simonnet; Pauline Lallemant-Dudek; Agnès Rigouzzo; Marie-Pierre Bonnet; Jean-Roch Fabreguettes; Jérôme Larghero; Jean-Marie Jouannic

doi:10.1016/j.gofs.2025.10.020

[PRIUM-Cell: In utero myelomeningocele prenatal repair program using mesenchymal stromal cells]

Gynecol Obstet Fertil Senol. 2025 Oct 22:S2468-7189(25)00368-X. doi: 10.1016/j.gofs.2025.10.020. Online ahead of print.

[Article in French]

Affiliations

¹ Service de médecine fœtale, hôpital Armand-Trousseau, AP-HP.Sorbonne université, DMU ORIGYNE, Paris, France; Unité de thérapie cellulaire, unité Inserm 1342, équipe Biotechnologie des cellules souches, centre d'investigation clinique en biothérapies, hôpital Saint-Louis, AP-HP, université Paris Cité, Paris, France; Centre de référence maladies rares Spin@, AP-HP. Sorbonne université, Paris, France. Electronic address: lucie.guilbaud@aphp.fr.
² Service de médecine fœtale, hôpital Armand-Trousseau, AP-HP.Sorbonne université, DMU ORIGYNE, Paris, France; Unité de thérapie cellulaire, unité Inserm 1342, équipe Biotechnologie des cellules souches, centre d'investigation clinique en biothérapies, hôpital Saint-Louis, AP-HP, université Paris Cité, Paris, France; Centre de référence maladies rares Spin@, AP-HP. Sorbonne université, Paris, France.
³ Unité de thérapie cellulaire, unité Inserm 1342, équipe Biotechnologie des cellules souches, centre d'investigation clinique en biothérapies, hôpital Saint-Louis, AP-HP, université Paris Cité, Paris, France.
⁴ Centre de référence maladies rares Spin@, AP-HP. Sorbonne université, Paris, France; Service de chirurgie orthopédique et réparatrice de l'enfant, hôpital Armand-Trousseau, AP-HP.Sorbonne université, Paris, France.
⁵ Centre de référence maladies rares Spin@, AP-HP. Sorbonne université, Paris, France; Service de radiologie pédiatrique, hôpital Armand-Trousseau, AP-HP.Sorbonne université, Paris, France.
⁶ Centre de référence maladies rares Spin@, AP-HP. Sorbonne université, Paris, France; Service de médecine physique et réadaptation pédiatrique, hôpital Armand-Trousseau, AP-HP.Sorbonne université, Paris, France.
⁷ Service d'anesthésie réanimation, hôpital Armand-Trousseau, AP-HP.Sorbonne université, DMU DREAM, Paris, France.
⁸ Centre MEARY de thérapie cellulaire et génique, hôpital Saint-Louis, AP-HP, Paris, France.
⁹ Service de médecine fœtale, hôpital Armand-Trousseau, AP-HP.Sorbonne université, DMU ORIGYNE, Paris, France; Centre de référence maladies rares Spin@, AP-HP. Sorbonne université, Paris, France.

PMID: 41135643
DOI: 10.1016/j.gofs.2025.10.020

Abstract

Background and rationale: Myelomeningocele (MMC), also known as Spina Bifida, is a congenital malformation of the spinal cord that results in a complex disability including motor deficits, sphincter disorders and cerebral anomalies. Benefit of fetal MMC surgery has been demonstrated since 2011, but remains partial, with persistent motor and sphincter disorders. We have developed an adjuvant treatment to improve spinal cord repair during fetal surgery: a patch composed of umbilical cord-derived mesenchymal stromal cells (UC-MSCs). Our in vitro and in vivo experiments in the ovine model of MMC demonstrated that the UC-MSC patch improves motor and urinary functions by promoting neuronal preservation in the spinal cord. We also confirmed the absence of maternal, fetal, and neonatal adverse effects. Our hypothesis is that this adjuvant therapy can similarly improve spinal cord repair in human fetuses, thereby improving clinical outcomes in affected children. The goal of the PRIUM-Cell clinical trial is to assess the use of UC-MSC patches as an adjuvant therapy during open fetal surgery for MMC in humans.

Study design and methods: This is an open-label study enrolling pregnant individuals with a fetus diagnosed with MMC located between spinal levels T1 and S1, associated with Chiari type 2 malformation. The allogeneic UC-MSC patch will contain 17 million UC-MSCs embedded in a semi-rigid scaffold. The patch will be applied directly to the fetal spinal cord during open fetal surgery performed between 23 and 26 weeks, following our center's standard protocol. Intensive maternal-fetal monitoring will be conducted for 7 days postoperatively during hospitalization, then weekly until delivery. The primary endpoint is successful completion of surgery with no neonatal adverse events. Secondary endpoints will be efficacy for the child at 8 weeks and 36 months, and safety for the mother from surgery to the postpartum period, and for the child up to 36 months of age.

Future directions: If our hypotheses are confirmed, we intend to conduct a Europe-wide phase III clinical trial.

Keywords: Cell therapy; Cellules stromales mésenchymateuses; Chirurgie in utero; Dysraphisme; Fetal surgery; Mesenchymal stromal cells; Myelomeningocele; Spina bifida; Thérapie cellulaire.

Publication types

English Abstract