Université Paris Cité, INSERM, U976 et Centre d'Investigation Clinique en Biothérapies CIC-BT CBT501, INSERM, Paris, France.
Service de médecine fœtale, APHP, Hôpital Trousseau, DMU ORIGYNE, Sorbonne Université, Paris, France.
BJOG. 2024 May;131(6):759-767. doi: 10.1111/1471-0528.17624. Epub 2023 Jul 26.
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.
MMC defects were surgically created at 75 days of gestation and repaired 14 days later.
Ovine MMC model: fetal lambs.
We compared lambs that received a UC-MSC patch with a control group of lambs that received an acellular patch.
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.
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/mm, P < 0.001). No tumours were observed.
Fetal repair of MMC using UC-MSC patches improves motor and sphincter function as well as spinal preservation and reduction of fibrosis.
研究胎儿手术中应用同种异体脐带间充质基质细胞（UC-MSC）贴片对羊膜束带综合征（MMC）模型运动和括约肌功能的影响。
在妊娠 75 天时通过手术制造 MMC 缺陷，并在 14 天后进行修复。
羊膜束带综合征模型：胎儿羔羊。
我们比较了接受 UC-MSC 贴片治疗的羔羊与接受无细胞贴片治疗的对照组羔羊。
在出生后 2 小时和 24 小时进行临床神经评估，包括已在羊膜束带综合征模型中验证的 Sheep Locomotor Rating scale（SLR）评分。还进行了电生理检查、脊柱扫描和组织学分析。
在 13 只接受手术的羔羊中，有 9 只存活分娩：其中 5 只接受了 UC-MSC 贴片治疗，4 只接受了无细胞贴片治疗。在 24 小时时，UC-MSC 组的羔羊评分明显更高（14 分比 5 分，P=0.04）。对照组中明显更常见的是肌无力（75%比 0%，P=0.02）。对照组的所有羔羊均失禁，而 UC-MSC 组无一例失禁。在自发肌电图活动、神经传导或脊髓诱发电位方面，UC-MSC 组与对照组之间没有观察到显著差异。在显微镜检查中，UC-MSC 组脊髓与真皮之间（平均厚度 453μm 比 3921μm，P=0.03）和脊髓周围（平均厚度 47μm 比 158μm，P<0.001）的纤维化程度较轻。在 MMC 缺陷区域检查脊髓时，UC-MSC 组的大型神经元密度更高（14.5 个神经元/mm 比 5.6 个神经元/mm，P<0.001）。未观察到肿瘤。
胎儿手术中使用 UC-MSC 贴片修复 MMC 可改善运动和括约肌功能以及脊髓保存和纤维化减少。
