First‐In‐Human Application of Human Umbilical Cord‐Derived Extracellular Vesicles in Tethered Spinal Cord Release Surgery

ABSTRACT 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.