Introduction: Spinal cord injury (SCI) is a devastating disease characterized by extensive cellular death, axonal disruption and scar formation, leading to lifelong disability, muscle spasms, sensory deficits and autonomic disturbances. Currently, no definitive therapy has been established to fundamentally improve neurological deficits in late chronic SCI (disease duration >1 year), which is the most prevalent among SCI patients. Transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) is a promising therapeutic alternative and pilot studies have demonstrated that hUC-MSCs can potentially improve neurological dysfunction with minimal adverse events. However, compared with other phase of SCI, neurological dysfunction in late chronic SCI is more challenging to recover, as the severity of SCI tends to stabilize at one year after the initial injury. For these reasons, this clinical study aims to evaluate the safety and efficacy of subarachnoid transplantation of hUC-MSCs in patients with late chronic SCI.

Methods and Analysis: This is a prospective, multicenter, open-label, single-arm clinical study involving 43 adult patients with late chronic SCI. Participants will receive four consecutive subarachnoid infusions of hUC-MSCs (1.0×10⁶ cells/kg), and will be regularly follow-up for four times, scheduled at 1, 3, 6, and 12 months after final hUC-MSCs transplantation. Safety will be assessed through the incidence and severity of adverse events (AEs) and serious adverse events (SAEs). Efficacy will be evaluated primarily by changes in the American Spinal Injury Association (ASIA) total score at 12 months post final transplantation. Secondary endpoints include ASIA impairment scale (AIS), Spinal Cord Independence Measure-III, muscle spasms, bladder and bowel function, and neurophysiological assessments.

Ethics and Dissemination: Ethical approval was obtained from the Institutional Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University and West China Hospital. Written informed consent will be obtained from all participants. This clinical study strictly adheres to the Declaration of Helsinki and Good Clinical Practice guidelines. Results will be disseminated through peer-reviewed publications and conference presentations, ensuring transparency and broad dissemination of findings.

Introduction: Spinal cord injury (SCI) is a devastating disease characterized by extensive cellular death, axonal disruption and scar formation, leading to lifelong disability, muscle spasms, sensory deficits and autonomic disturbances. Currently, no definitive therapy has been established to fundamentally improve neurological deficits in late chronic SCI (disease duration >1 year), which is the most prevalent among SCI patients. Transplantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) is a promising therapeutic alternative and pilot studies have demonstrated that hUC-MSCs can potentially improve neurological dysfunction with minimal adverse events. However, compared with other phase of SCI, neurological dysfunction in late chronic SCI is more challenging to recover, as the severity of SCI tends to stabilize at one year after the initial injury. For these reasons, this clinical study aims to evaluate the safety and efficacy of subarachnoid transplantation of hUC-MSCs in patients with late chronic SCI.

Methods and Analysis: This is a prospective, multicenter, open-label, single-arm clinical study involving 43 adult patients with late chronic SCI. Participants will receive four consecutive subarachnoid infusions of hUC-MSCs (1.0×10⁶ cells/kg), and will be regularly follow-up for four times, scheduled at 1, 3, 6, and 12 months after final hUC-MSCs transplantation. Safety will be assessed through the incidence and severity of adverse events (AEs) and serious adverse events (SAEs). Efficacy will be evaluated primarily by changes in the American Spinal Injury Association (ASIA) total score at 12 months post final transplantation. Secondary endpoints include ASIA impairment scale (AIS), Spinal Cord Independence Measure-III, muscle spasms, bladder and bowel function, and neurophysiological assessments.

Ethics and Dissemination: Ethical approval was obtained from the Institutional Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University and West China Hospital. Written informed consent will be obtained from all participants. This clinical study strictly adheres to the Declaration of Helsinki and Good Clinical Practice guidelines. Results will be disseminated through peer-reviewed publications and conference presentations, ensuring transparency and broad dissemination of findings.