Clinical Trial Evaluates Safety of iPSC-Derived Neural Stem Cells for Spinal Cord Injury

A phase 1 clinical study conducted at Keio University in Tokyo has assessed the safety of transplanting human induced pluripotent stem cell-derived neural stem/progenitor cells (iPSC-NS/PCs) into patients with subacute, complete traumatic spinal cord injuries (SCI). The study, which received oversight from the Japanese Ministry of Health, Labour and Welfare, sought to determine if these cells could be safely administered to patients with AIS grade A injuries between 14 and 28 days post-injury. According to the Japan Registry of Clinical Trials, the research focused on safety as the primary endpoint, with secondary evaluations covering neurological and functional recovery.

Cell Preparation and Transplantation Protocol

The study utilized a specific human iPSC line, YZWJs513, which was established under Good Manufacturing Practice (GMP) conditions by the Center for iPS Cell Research and Application at Kyoto University. Researchers differentiated these cells into NS/PCs using the serum-free embryoid body-like aggregates (SFEBq) protocol. The final product, designated ONH-iPSNPC-003, underwent rigorous quality control to ensure chromosomal normality and the absence of undifferentiated cells or tumorigenic genomic mutations. Before transplantation, the cells were treated with a γ-secretase inhibitor (DAPT) to suppress Notch signaling, a process intended to promote neural differentiation.

During the surgical procedure, surgeons injected approximately 2.0 × 10⁶ cells directly into the spinal cord injury epicenter. Patients were placed on a regimen of tacrolimus to suppress immune rejection, starting one day before the procedure and continuing for nine months post-transplantation. This immunosuppressive protocol was monitored through regular blood trough level assessments.

Safety Monitoring and Clinical Assessment

Because the study involved a first-in-human application of these specific cells, an independent data-monitoring committee reviewed the initial participant’s status at the three-month mark before proceeding with subsequent enrollments.

To identify potential tumor formation—a primary concern with pluripotent-derived therapies—the clinical team conducted serial non-contrast MRI scans of the cervical spine. The imaging protocols focused on detecting mass-forming lesions or infiltrative signal abnormalities. Additionally, 18F-FDG PET imaging was performed 24 weeks post-transplantation to evaluate the metabolic activity of the grafted site, with results compared against established physiological uptake levels for the spinal cord.

Comparative Analysis and Study Context

The research team performed an exploratory comparison using data from the Japanese Spinal Cord Injury Database (JSSCI-DB). By selecting a historical cohort of patients with similar injury characteristics—specifically AIS grade A status at two weeks post-injury and injury levels between C4 and C8—the investigators aimed to contextualize the neurological outcomes observed in the trial participants. The study adhered to standard Japanese national health insurance rehabilitation guidelines, providing up to three hours of daily therapy in the initial months, without the use of advanced robotic-assisted devices or electrical stimulation.

Key Considerations for Regenerative Medicine

• Regulatory Compliance: The trial was conducted in accordance with the Act on the Safety of Regenerative Medicine in Japan, with approval from the Certified Committee for Regenerative Medicine at Keio University.
• Long-term Oversight: Participants are subject to a long-term observational follow-up study registered under UMIN000050104, ensuring extended surveillance for graft-related complications.
• Inclusion Criteria: The study strictly limited participation to those with complete motor and sensory loss (AIS grade A) and excluded patients with multiple-site injuries, dural ruptures, or major systemic comorbidities.

This phase 1 trial provides foundational data on the safety profile of iPSC-NS/PC transplantation in a clinical setting. As the field of regenerative medicine progresses, the long-term data from this cohort will be essential for determining the viability of stem cell-based interventions for severe spinal cord injuries.