iPSC-Derived Neural Stem/Progenitor Cells Transplanted into 4 Patients With Complete Cervical Spinal Cord Injury: 2–4 Years of Safety Follow-Up
Background
A phase 1 trial of induced pluripotent stem cell (iPSC)-derived neural stem/progenitor cell transplantation in four patients with subacute complete cervical spinal cord injury met its 52-week safety endpoint. Follow-up totaling 2–4 years per patient revealed no tumors or adverse events related to the transplanted cells. Adverse events related to surgery and immunosuppressive medication did occur, and the study could not determine whether the observed functional improvements resulted from cell transplantation.
In spinal cord injury, decompression and stabilization surgery and rehabilitation have limited ability to rebuild damaged neural circuits. In earlier animal studies, the researchers observed recovery of motor function after transplantation of iPSC-derived neural stem/progenitor cells. Could similar results be obtained in humans? The risks of abnormal cell growth, surgery within the spinal cord, and immunosuppression first needed to be assessed. Published in Nature Medicine, this first-in-human trial prioritized assessment of these safety issues.
Key Findings
The study used a single-arm, open-label design with no control group. All participants were Japanese men aged 26–66 years, with neurological injury levels of C4–C6. On the day of transplantation, their American Spinal Injury Association Impairment Scale (AIS) grade was reconfirmed as A. This denotes a neurologically complete injury, with no preserved sensation in the lowest sacral segments, S4–S5, or specified anal sensory and motor functions. It does not mean that the spinal cord was anatomically severed; transection injuries were excluded from this trial.
The researchers differentiated iPSCs generated from a healthy donor’s umbilical cord blood into neural stem/progenitor cells. Between 15 and 27 days after injury, each patient received a single injection of 2 million cells into the injury epicenter. The immunosuppressant tacrolimus was started the day before transplantation, continued for six months, and then scheduled to be tapered and discontinued by month nine. Participants also received rehabilitation within the standard range.
The primary endpoint was safety during the 52-week intervention period, assessed by the severity of all adverse events and their relationship to the cells, surgery, or immunosuppression. There were 84 adverse-event occurrences in total, with repeat events counted separately. Moderate surgery-related events were increased upper-airway secretions and cerebrospinal fluid leakage. A total of 22 mild or moderate events were considered related to tacrolimus.
One episode of transient hyperkalemia met the definition of a serious adverse event. It resolved spontaneously without symptoms, and the researchers considered a blood-sampling artifact more likely than a true clinical abnormality. No serious adverse events were attributed to the transplanted cells.
Magnetic resonance imaging (MRI) during the 52-week intervention period and positron emission tomography (PET) at 24 weeks after transplantation showed no findings suggestive of abnormal cell growth. Observation continued, with total follow-up of 2, 2.5, 3, and 4 years for the four patients. No tumors, imaging abnormalities related to the transplanted cells, or unexpected neurological deterioration were identified during this period.
In exploratory functional assessments, the median improvement in motor score from baseline at 52 weeks was 13 points, with individual improvements ranging from 10 to 40 points. Two patients changed from AIS grade A to grades C and D, respectively. The numerical improvements were greater than those in data from previously registered patients, but this was not a randomized controlled comparison. Natural recovery and differences in patient selection cannot be ruled out, so the improvements cannot be established as a treatment effect.
Meaning and Outlook
The study indicated the clinical feasibility of administering quality-controlled allogeneic iPSC-derived cells into the spinal cord and conducting follow-up. However, the absence of visible tumors on imaging does not establish cell survival, differentiation, or integration into neural circuits. The researchers stated that they could not directly confirm these outcomes.
The small sample of four participants, all Japanese men, limits how broadly the results can be generalized. Long-term surveillance must also continue to assess delayed tumor development and chronic immune-related risks. Subsequent controlled trials will need to establish the causal relationship and durability of functional improvements and evaluate the overall risks and benefits, including invasive surgery and immunosuppression.
The study design and results are based on the provided full-text paper.
Nature Medicine, Published online: 21 July 2026; doi:10.1038/s41591-026-04549-6A phase 1 trial evaluating the safety of iPSC-derived neural stem cell transplantation in subacute complete spinal cord injury, with 2–4 years of follow-up including MRI, neurological and functional assessments met its primary outcome.
For researchers designing subsequent cell-therapy trials for spinal cord injury, this report offers a practical example linking cell manufacturing, administration, and safety monitoring. Participants were assessed during the subacute phase, and cells were thawed four days before transplantation and cultured to allow recovery. Intraspinal administration was coordinated with immunosuppression and long-term imaging follow-up. Subsequent trials can use this as a reference when preparing manufacturing facilities alongside surgical, rehabilitation, and follow-up systems.
Clinical development must assess events related to surgery and immunosuppression as well as the absence of observed tumors. The next questions are whether functional improvement exceeds natural recovery and whether the clinical benefit justifies the risks. The current results alone cannot establish a standard of care or determine the prospects for regulatory approval or a reduction in caregiving burden.