Novel artificial nerve transplantation of human iPSC-derived neurite bundles enhanced nerve regeneration after peripheral nerve injury.

BACKGROUND: Severe peripheral nerve damage always requires surgical treatment. Autologous nerve transplantation is a standard treatment, but it is not sufficient due to length limitations and extended surgical time. Even with the available artificial nerves, there is still large room for improvement in their therapeutic effects. Novel treatments for peripheral nerve injury are greatly expected. METHODS: Using a specialized microfluidic device, we generated artificial neurite bundles from human iPSC-derived motor and sensory nerve organoids. We developed a new technology to isolate cell-free neurite bundles from spheroids. Transplantation therapy was carried out for large nerve defects in rat sciatic nerve with novel artificial nerve conduit filled with lineally assembled sets of human neurite bundles. Quantitative comparisons were performed over time to search for the artificial nerve with the therapeutic effect, evaluating the recovery of motor and sensory functions and histological regeneration. In addition, a multidimensional unbiased gene expression profiling was carried out by using next-generation sequencing. RESULT: After transplantation, the neurite bundle-derived artificial nerves exerted significant therapeutic effects, both functionally and histologically. Remarkably, therapeutic efficacy was achieved without immunosuppression, even in xenotransplantation. Transplanted neurite bundles fully dissolved after several weeks, with no tumor formation or cell proliferation, confirming their biosafety. Posttransplant gene expression analysis highlighted the immune system's role in recovery. CONCLUSION: The combination of newly developed microfluidic devices and iPSC technology enables the preparation of artificial nerves from organoid-derived neurite bundles in advance for future treatment of peripheral nerve injury patients. A promising, safe, and effective peripheral nerve treatment is now ready for clinical application.

Combinational Treatment Involving Decellularized Extracellular Matrix Hydrogels With Mesenchymal Stem Cells Increased the Efficacy of Cell Therapy in Pancreatitis.

Cell transplantation using mesenchymal stem cells (MSCs) has emerged as a promising approach to repairing and regenerating injured or impaired organs. However, the survival and retention of MSCs following transplantation remain a challenge. Therefore, we investigated the efficacy of co-transplantation of MSCs and decellularized extracellular matrix (dECM) hydrogels, which have high cytocompatibility and biocompatibility. The dECM solution was prepared by enzymatic digestion of an acellular porcine liver scaffold. It could be gelled and formed into porous fibrillar microstructures at physiological temperatures. MSCs expanded three-dimensionally in the hydrogel without cell death. Compared to the 2-dimensional cell culture, MSCs cultured in the hydrogel showed increased secretion of hepatocyte growth factor (HGF) and tumor necrosis factor-inducible gene 6 protein (TSG-6), both of which are major anti-inflammatory and anti-fibrotic paracrine factors of MSCs, under TNFα stimulation. In vivo experiments showed that the co-transplantation of MSCs with dECM hydrogel improved the survival rate of engrafted cells compared to those administered without the hydrogel. MSCs also demonstrated therapeutic effects in improving inflammation and fibrosis of pancreatic tissue in a dibutyltin dichloride (DBTC)-induced rat pancreatitis model. Combinational use of dECM hydrogel with MSCs is a new strategy to overcome the challenges of cell therapy using MSCs and can be used for treating chronic inflammatory diseases in clinical settings.

Association between time to surgery and 90-day mortality after hip fracture: A retrospective cohort study of 1734 cases.

BACKGROUND: It remains unclear whether early surgical intervention can reduce mortality after surgery in hip fracture patients. The aim of this study was to investigate the association between time from injury to surgery and mortality rate within 90 days after hip fracture surgery. METHODS: We retrospectively identified 1827 patients who underwent hip fracture surgery in a tertiary care center in Japan between April 2007 and March 2017. After applying exclusion criteria (patients with spontaneous fracture, multiple fractures, revision surgery, total hip arthroplasty, or a refusal to participate), 1734 patients were included. We extracted data concerning patients' age, race, sex, operative procedure, American Society of Anesthesiologists (ASA) score, days from injury to surgery (injury-surgery days), and days from admission to surgery (admission-surgery days), which could affect 90-day mortality after surgery. Variables associated with 90-day mortality were determined using multivariate logistic regression analysis. RESULTS: The 90-day postoperative mortality rate was 3.5% (60 of 1734). Multivariable analysis showed that injury-surgery days were not associated with 90-day mortality (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.80 to 1.05; P = 0.19), and that older age (OR, 1.06; 95% CI, 1.02 to 1.10; P = 0.005), male sex (OR, 3.62; 95% CI, 1.86 to 7.03; P < 0.001) and high ASA score (OR, 2.10; 95% CI, 1.06 to 4.18; P = 0.034) significantly increased 90-day mortality. In addition, admission-surgery days were not associated with 90-day mortality (OR, 0.95; 95% CI, 0.83 to 1.09; P = 0.45). CONCLUSION: Our results demonstrated that time from injury to surgery was not associated with mortality within 90 days after surgery after adjusting for age, sex, operative procedure, and ASA score.

Pacemaker Lead Dislodgement Due to Left Shoulder Dislocation: A Case Report.

CASE: A 63-year-old man with a cardiac pacemaker presented with a left shoulder dislocation. His heart rate was 46 beats per minute, and pacemaker testing demonstrated an elevated pacing threshold, a decreased sensing threshold, and stable pacemaker lead impedance. Lead dislodgement due to the shoulder dislocation was suspected, and the patient underwent repositioning of the lead. CONCLUSION: When a patient with a pacemaker dislocates a shoulder, it should be confirmed that the heart rate is above the programmed lower rate of the pacemaker; electrocardiography should be performed, and the pacing parameters should be checked to ensure that pacing failure is not overlooked.