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.
METHODS: MMC defects were surgically created at 75 days of gestation and repaired 14 days later.
METHODS: 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.
METHODS: 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.
METHODS: MMC defects were surgically created at 75 days of gestation and repaired 14 days later.
METHODS: 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.
METHODS: 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.
摘要：
目的：研究胎儿手术中应用同种异体脐带间充质基质细胞（UC-MSC）补片对绵羊MMC模型运动和括约肌功能的影响。
方法：在妊娠75天时手术产生MMC缺损，14天后修复。
方法：绵羊MMC模型：胎儿羔羊。
方法：我们比较了接受UC-MSC贴片的羔羊与接受无细胞贴片的对照组羔羊。
方法：在生命的2和24小时进行临床神经学评估，包括测定绵羊运动量表（SLR），这已经在绵羊MMC模型中得到了验证。电身体检查,还进行了脊柱扫描和组织学分析。
结果：在13只手术羔羊中，9人活着出生:其中5人接受了UC-MSC贴剂,4人接受了无细胞贴剂.在生命的24小时里，UC-MSC组的羔羊得分明显较高(14对5,P=0.04).肌萎缩在对照组中明显更常见（75％对0％，P=0.02)。对照组的所有羔羊和UC-MSC组的羔羊均未出现失禁。UC-MSC和对照组在自发性EMG活动的存在方面没有观察到显著差异,神经传导或脊髓诱发电位。在显微镜检查中，UC-MSC组的羔羊在脊髓和真皮之间的纤维化较少(平均厚度，453与3921μm，P=0.03）和脊髓周围（平均厚度，47对158μm，P<0.001)。对MMC缺损区域的脊髓检查显示，UC-MSC组中较大的神经元密度较高（14.5对5.6个神经元/mm2，P<0.001)。没有观察到肿瘤。
结论：使用UC-MSC贴剂修复胚胎MMC可改善运动和括约肌功能，并可保留脊柱和减少纤维化。
方法：在妊娠75天时手术产生MMC缺损，14天后修复。
方法：绵羊MMC模型：胎儿羔羊。
方法：我们比较了接受UC-MSC贴片的羔羊与接受无细胞贴片的对照组羔羊。
方法：在生命的2和24小时进行临床神经学评估，包括测定绵羊运动量表（SLR），这已经在绵羊MMC模型中得到了验证。电身体检查,还进行了脊柱扫描和组织学分析。
结果：在13只手术羔羊中，9人活着出生:其中5人接受了UC-MSC贴剂,4人接受了无细胞贴剂.在生命的24小时里，UC-MSC组的羔羊得分明显较高(14对5,P=0.04).肌萎缩在对照组中明显更常见（75％对0％，P=0.02)。对照组的所有羔羊和UC-MSC组的羔羊均未出现失禁。UC-MSC和对照组在自发性EMG活动的存在方面没有观察到显著差异,神经传导或脊髓诱发电位。在显微镜检查中，UC-MSC组的羔羊在脊髓和真皮之间的纤维化较少(平均厚度，453与3921μm，P=0.03）和脊髓周围（平均厚度，47对158μm，P<0.001)。对MMC缺损区域的脊髓检查显示，UC-MSC组中较大的神经元密度较高（14.5对5.6个神经元/mm2，P<0.001)。没有观察到肿瘤。
结论：使用UC-MSC贴剂修复胚胎MMC可改善运动和括约肌功能，并可保留脊柱和减少纤维化。
