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

Abstract

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 < 0.001). Examination of the spinal cord in the area of the MMC defect showed a higher large neuron density in the UC-MSC group (14.5 versus 5.6 neurons/mm², P < 0.001). No tumours were observed.

Conclusions: Fetal repair of MMC using UC-MSC patches improves motor and sphincter function as well as spinal preservation and reduction of fibrosis.

Keywords: fetal surgery; motor function; myelomeningocele; ovine model; spinal cord preservation; umbilical cord mesenchymal stem cells.