Allogenic umbilical cord‐derived mesenchymal stromal cells improve motor function in prenatal surgical repair of myelomeningocele: An ovine model study

• Published in: BJOG : an international journal of obstetrics and gynaecology 2024-05, Vol.131 (6), p.759-767
• Main Authors: Athiel, Yoann, Jouannic, Jean‐Marie, Mauffré, Vincent, Dehan, Coralie, Adam, Clovis, Blot, Stéphane, Lallemant, Pauline, De Saint Denis, Timothé, Larghero, Jérôme, Nasone, Justine, Guilbaud, Lucie
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Dermis; Female; fetal surgery; Fetuses; Fibrosis; Humans; Life Sciences; Meningomyelocele - surgery; Mesenchymal stem cells; Mesenchymal Stem Cells - pathology; Mesenchymal Stem Cells - physiology; Motor ability; motor function; myelomeningocele; Nerve conduction; Neurosurgery; ovine model; Pregnancy; Sheep; Sphincter; Spinal cord; Spinal Cord - pathology; spinal cord preservation; Spine; Stem cells; Stromal cells; Umbilical Cord; umbilical cord mesenchymal stem cells
• ISSN: 1470-0328; 1471-0528
• DOI: 10.1111/1471-0528.17624

Objective To investigate the effects of an adjuvant allogenic umbilical cord mesenchymal stromal cell (UC‐MSC) patch applied during fetal surgery on motor and sphincter function in the ovine MMC model. Design MMC defects were surgically created at 75 days of gestation and repaired 14 days later. Population Ovine MMC model: fetal lambs. Methods We compared lambs that received a UC‐MSC patch with a control group of lambs that received an acellular patch. Main Outcome Measures Clinical neurological assessment was performed at 2 and 24 hours of life and included determination of the Sheep Locomotor Rating scale (SLR), which has been validated in the ovine MMC model. Electrophysical examinations, spine scans and histological analyses were also performed. Results Of the 13 operated lambs, nine were born alive: five had of these had received a UC‐MSC patch and four an acellular patch. At 24 hours of life, lambs in the UC‐MSC group had a significantly higher score (14 versus 5, P = 0.04). Amyotrophy was significantly more common in the control group (75% versus 0%, P = 0.02). All the lambs in the control group and none of those in the UC‐MSC group were incontinent. No significant differences were observed between the UC‐MSC and control groups in terms of the presence of spontaneous EMG activity, nerve conduction or spinal evoked potentials. In the microscopic examination, lambs in the UC‐MSC group had less fibrosis between the spinal cord and the dermis (mean thickness, 453 versus 3921 μm, P = 0.03) and around the spinal cord (mean thickness, 47 versus 158 μm, P