Krause Matthias, Gburek-Augustat Janina, Gräfe Daniel, Metzger Roman, Ginzel Marco, Griessenauer Christoph J, Grassner Lukas, Weghuber Daniel, Gradl Johann, Auer Daniela, Schally Tanja, Rund Stefan, Kals Carina, Folie Christina, Bayer Elisabeth, Gimona Mario, Rohde Eva
Department for Neurosurgery, Christian-Doppler-Klinik, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
Department of Pediatric Surgery, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
J Extracell Vesicles. 2025 Jun;14(6):e70104. doi: 10.1002/jev2.70104.
Spina bifida is a congenital neural tube defect that has a high risk of secondary neurological deterioration due to tethering of the spinal cord. We present the first application of human umbilical cord-derived mesenchymal stromal cell-derived extracellular vesicle (UC-MSC-EV) therapy in humans during spina bifida surgery. We discuss the application, post-operative outcome and highlight the potential of extracellular vesicle therapy in the management of spina bifida. Administration of extracellular vesicles containing therapeutically active agents has emerged as a potential new treatment modality for neurological disorders. By direct intrathecal application during surgery, UC-MSC-EVs can deliver therapeutic payloads to target cells and the extracellular environment, offering a novel approach to neuroprotection and tissue repair. A 2-year-old girl diagnosed with spina bifida presented with progressive syringomyelia as sign of secondary tethered cord syndrome with intramedullary dermoid inclusion tumour after postnatal spina bifida repair. After pre-operative assessment and multidisciplinary consultation, it was decided to proceed with spinal cord release surgery with the use of EV. During the surgical procedure, the tethered cord was released, dermoid and lipoma tissue were resected. Concurrently, UC-MSC-EVs were administered directly onto the released placode and spinal cord. Post-operative MRI demonstrated a good de-tethering effect and no medullary oedema. No adverse events were reported. The neurological deficit remained unchanged at 6 months follow-up examination. Intraoperative application of UC-MSC-EVs might be an option to ameliorate intrathecal scarring following spina bifida surgery. Whether EVs will result in significant effects for the long-term neurological outcome needs to be studied in randomised clinical trials.
脊柱裂是一种先天性神经管缺陷，由于脊髓栓系，继发神经功能恶化的风险很高。我们展示了人脐带间充质基质细胞衍生的细胞外囊泡（UC-MSC-EV）疗法在脊柱裂手术中的首次人体应用。我们讨论了其应用、术后结果，并强调了细胞外囊泡疗法在脊柱裂治疗中的潜力。含有治疗活性剂的细胞外囊泡的给药已成为治疗神经系统疾病的一种潜在新疗法。通过在手术期间直接鞘内应用，UC-MSC-EV可以将治疗性物质传递到靶细胞和细胞外环境，为神经保护和组织修复提供了一种新方法。一名2岁被诊断为脊柱裂的女孩，在出生后脊柱裂修复术后，出现进行性脊髓空洞症，这是继发脊髓栓系综合征并伴有髓内皮样包涵体肿瘤的迹象。经过术前评估和多学科会诊，决定在使用EV的情况下进行脊髓松解手术。在手术过程中，松解了栓系的脊髓，切除了皮样和脂肪瘤组织。同时，将UC-MSC-EV直接应用于松解后的神经板和脊髓上。术后MRI显示松解效果良好，无髓内水肿。未报告不良事件。在6个月的随访检查中，神经功能缺损保持不变。术中应用UC-MSC-EV可能是改善脊柱裂手术后鞘内瘢痕形成的一种选择。EVs是否会对长期神经功能结果产生显著影响，需要在随机临床试验中进行研究。
