Purpose

Augmentation of in utero myelomeningocele repair with human placental mesenchymal stromal cells seeded onto extracellular matrix (PMSC-ECM) improves motor outcomes in an ovine myelomeningocele model. This study evaluated the safety of PMSC-ECM application directly onto the fetal spinal cord in preparation for a clinical trial.

Methods

Laminectomy of L5-L6 with PMSC-ECM placement directly onto the spinal cord was performed in five fetal lambs at gestational age (GA) 100–106 days. Lambs and ewes were monitored for three months following delivery. Lambs underwent magnetic resonance imaging (MRI) of the brain and spine at birth and at three months. All organs from lambs and uteri from ewes underwent histologic evaluation. Lamb spinal cords and brains and ewe placentas were evaluated for persistence of PMSCs by polymerase chain reaction for presence of human DNA.

Results

MRIs demonstrated no evidence of abnormal tissue growth or spinal cord tethering. Histological analysis demonstrated no evidence of abnormal tissue growth or treatment related adverse effects. No human DNA was identified in evaluated tissues.

Conclusion

There was no evidence of abnormal tissue growth or PMSC persistence at three months following in utero application of PMSC-ECM to the spinal cord. This supports proceeding with clinical trials of PMSC-ECM for in utero myelomeningocele repair.

Level of evidence

N/A

Type of study

Basic science

中文翻译：

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胎盘间充质基质细胞在新型绵羊模型中子宫内修复脊髓脊膜膨出的长期安全性评估

目的

用接种到细胞外基质 (PMSC-ECM) 上的人胎盘间充质基质细胞增强子宫内脊髓脊膜膨出修复，改善绵羊脊髓脊膜膨出模型的运动结果。本研究评估了 PMSC-ECM 直接应用于胎儿脊髓的安全性，为临床试验做准备。

方法

对五只胎龄 (GA) 100-106 天的胎儿羔羊进行了 L5-L6 的椎板切除术，PMSC-ECM 直接放置在脊髓上。羔羊和母羊在分娩后被监测三个月。羔羊在出生和三个月时接受了大脑和脊柱的磁共振成像 (MRI)。羔羊的所有器官和母羊的子宫都进行了组织学评估。通过聚合酶链反应检测人类 DNA 的存在，评估羔羊脊髓和大脑以及母羊胎盘的 PMSC 持久性。

结果

MRI 显示没有异常组织生长或脊髓束缚的证据。组织学分析表明没有异常组织生长或治疗相关不良反应的证据。在评估的组织中没有发现人类 DNA。

结论

在子宫内将 PMSC-ECM 应用于脊髓后三个月，没有异常组织生长或 PMSC 持续存在的证据。这支持继续进行 PMSC-ECM 用于子宫内脊髓脊膜膨出修复的临床试验。

证据等级

不适用

学习类型

基础科学