Since the advent of induced pluripotent stem cells (iPSCs), clinical trials using iPSC-based cell transplantation therapy have been performed in various fields of regenerative medicine. We previously demonstrated that the transplantation of mouse iPSC-derived neurospheres containing neural stem/progenitor cells with bioabsorbable nerve conduits promoted nerve regeneration in the long term in murine sciatic nerve defect models. However, it remains unclear how long the grafted iPSC-derived neurospheres survived and worked after implantation. In this study, the long-term survival of the transplanted mouse iPSC-derived neurospheres with nerve conduits was evaluated in high-immunosuppressed or non-immunosuppressed mice using in vivo imaging for the development of iPSC-based cell therapy for peripheral nerve injury. Complete 5-mm long defects were created in the sciatic nerves of immunosuppressed and non-immunosuppressed mice and reconstructed using nerve conduits coated with iPSC-derived neurospheres labeled with ffLuc. The survival of mouse iPSC-derived neurospheres on nerve conduits was monitored using in vivo imaging. The transplanted iPSC-derived neurospheres with nerve conduits survived for 365 days after transplantation in the immunosuppressed allograft models, but only survived for at least 14 days in non-immunosuppressed allograft models. This is the first study to find the longest survival rate of stem cells with nerve conduits transplanted into the peripheral nerve defects using in vivo imaging and demonstrates the differences in graft survival rate between the immunosuppressed allograft model and immune responsive allograft model. In the future, if iPSC-derived neurospheres are successfully transplanted into peripheral nerve defects with nerve conduits using iPSC stock cells without eliciting an immune response, axonal regeneration will be induced due to the longstanding supportive effect of grafted cells on direct remyelination and/or secretion of trophic factors.

BACKGROUND: We previously demonstrated that a bioabsorbable nerve conduit coated with mouse induced pluripotent stem cell (iPSC)-derived neurospheres accelerated peripheral nerve regeneration in mice. OBJECTIVE: We examined the fate and utility of iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve gaps in mice. METHODS: Complete 5-mm defects were created in sciatic nerves and reconstructed using nerve conduits that were either uncoated or coated with mouse iPSC-derived neurospheres. The survival of the neurospheres on the nerve conduits was tracked using an in vivo imaging. The localization of the transplanted cells and regenerating axons was examined histologically. The gene expression levels in the nerve conduits were evaluated. RESULTS: The neurospheres survived for at least 14 days, peaking at 4--7 days after implantation. The grafted neurospheres remained as Schwann-like cells within the nerve conduits and migrated into the regenerated axons. The expression levels of ATF3, BDNF, and GDNF in the nerve conduit coated with neurospheres were upregulated. CONCLUSIONS: Mouse iPSC-derived neurospheres transplanted with nerve conduits for the treatment of sciatic nerve defects in mice migrated into regenerating axons, survived as Schwann-like cells, and promoted axonal growth with an elevation in the expression of nerve regeneration-associated trophic factors.

Talus fracture is relatively rare in adults. Furthermore, talus fracture in pediatric population is rarer than in adult population. Although undisplaced talus fractures can be treated conservatively, most of talus fractures with displacement require surgical treatment in both pediatric and adult patients. In addition, avascular necrosis and arthrosis are the main complications of displaced talus fracture. A 14-year-old boy was referred to our hospital owing to foot injury sustained on jumping off about 10 stairs. Highly displaced talus body fracture of the dome and the posterior process. Because the Linhart classification of this case was III-C and instability at the fracture site persisted even after closed reduction, we performed arthroscopic-assisted reduction and internal fixation (ARIF) using headless screws and an external fixator under general anesthesia. We removed the external fixator at 3 months after the surgery. At the 1-year follow-up, the patient was able to walk with full weight bearing and his Japanese Orthopaedic Association score recovered from 9 points before the surgery to 95 points. The range of motion of dorsiflexion and plantarflexion was 10° and 60°, respectively, which were similar to that on the left side. No signs of bone necrosis or arthrosis were observed on imaging. ARIF with external fixation might be the treatment of choice for such a case.

Hamate hook fractures are usually caused by direct trauma while using a tennis racket or a baseball bat. We report stress fracture of the hamate hook in a water polo player without any specific trauma. We consider that the stress fracture occurred via indirect mechanisms through the flexor tendons. Strong ulnar deviation of the wrist during ball release and strong grip on a ball with outstretched fingers, which are unique to water polo, were the likely causes of the stress fracture of the hamate hook.

A number of outcome predictors for carpal tunnel release (CTR) for carpal tunnel syndrome (CTS) have been reported. However, some predictors are controversial, and few studies have referred to the early postoperative outcome prognostic factors after CTR. The aim of this study was to investigate whether pain and numbness at 1 month post-CTR were early postoperative predictors of clinical outcomes 6 months after surgery. Pain and numbness were evaluated using the visual analog scale (VAS) preoperatively and at 1 month post-surgery. Patient-reported outcome measures (PROMs), including the Quick Disabilities of the Arm, Shoulder and Hand (QDASH) measure, the Hand20 questionnaire and the Boston Carpal Tunnel Questionnaire (BCTQ), were recorded for each patient 6 months after surgery. The BCTQ consisted of the Symptom Severity Scale (SSS) and Functional Status Scale (FSS). Multivariable linear regression analysis was performed to investigate the association between the VAS scores and PROMs. We retrospectively identified 93 patients who underwent open carpal tunnel release (OCTR) or endoscopic carpal tunnel release. The mean age of the patients was 67.5 years, and 67 patients (72.0%) were female. Sixty patients were treated by OCTR (65.0%). With multivariable linear regression analysis, we found that pain and numbness, evaluated with VAS 1 month post-surgery had significant correlations with QDASH, Hand20, SSS and FSS 6 months after surgery. In conclusion, pain and numbness 1 month after CTR predict PROMs at 6 months.