Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury.

Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.

Rupture of an adjacent cerebral aneurysm following the deployment of a Pipeline embolization device: illustrative case.

BACKGROUND: Although the Pipeline embolization device (PED) is effective for intracranial aneurysm treatment, its impact on the surrounding vascular structure is unknown. OBSERVATIONS: A 71-year-old woman was incidentally found to have a simultaneous large posterior communicating artery aneurysm and an ipsilateral small anterior choroidal artery aneurysm. She underwent flow diversion therapy for both aneurysms with a PED, but the distal shortening of the PED after deployment led to the exposure of the anterior choroidal artery aneurysm. Follow-up angiography revealed complete obliteration of the posterior communicating artery aneurysm, but the anterior choroidal artery aneurysm remained. Three years after the endovascular surgery, the patient experienced a subarachnoid hemorrhage due to the rupture of the anterior choroidal artery aneurysm. Retrospective analysis of angiographic images revealed a change in the vascular geometry surrounding the ruptured aneurysm after PED deployment; this was further accompanied by an increase in the flow velocity inside the aneurysm. LESSONS: Because PED use might induce the adverse effects on the adjacent uncovered aneurysm by changing the vascular geometry and hemodynamic stress, a cautious therapeutic strategy, such as proper placement of the stent and using a longer and appropriate-sized PED, should be chosen when deploying the PED.

Direct Inspection with Dual Endoscope Technique via Bilateral Transforaminal Approach Leading to Complete Resection of Recurrent Colloid Cyst of the Third Ventricle.

BACKGROUND: Although endoscopic approaches are widely used for resection of colloid cysts because of the lower invasiveness, removal of the recurrent colloid cyst is still challenging. Total removal is sometimes difficult to achieve with single-port endoscopy because of the restricted access and working space. To compensate for these limitations, the dual endoscope technique via the bilateral transforaminal approach was chosen. CASE DESCRIPTION: A 34-year-old woman with recurrent colloid cyst of the third ventricle was admitted to our department. She had a history of endoscopic subtotal removal at another institution. Reoperation was scheduled and the endoscopic bilateral transforaminal approach was chosen to ensure total removal with minimum complication risk. After decompression, the cyst was retracted toward the third ventricle floor via the right foramen of Monro. Under direct inspection with an angled scope via the right foramen of Monro, the cyst attachment on the third ventricle roof was sharply dissected via the left foramen of Monro, resulting in total removal. CONCLUSIONS: The dual endoscope technique via the bilateral transforaminal approach can achieve better surgical outcome by obtaining direct visualization of the cyst attachment. Although the indication should be limited, this approach can be considered especially for patients with recurrent lesions involving possible adhesion to vital structures.

Reducing Surgeon's Physical Stress in Minimally Invasive Neurosurgery.

BACKGROUND AND STUDY AIMS: Various minimally invasive approaches are used in neurosurgery. Surgeons must perform nondynamic fine movements in a narrow corridor, so specially designed surgical devices are essential. Unsophisticated instruments may pose potential hazards. The purpose of this study was to assess the factors associated with muscle fatigue during minimally invasive neurosurgery and to investigate whether physical stress can be reduced by refining the devices used. MATERIAL AND METHODS: Four physical aspects of a handpiece were investigated: torque of conduits (0.20, 0.28, and 0.37 kgf*cm), shape of hand grip (five types), angle of the nozzle (0, 20, and 40 degrees), and weight balance (neutral, proximal, and distal). To evaluate muscle fatigue, surface electromyography was recorded from the extensor carpi radialis muscle and flexor carpi radialis muscle during a geometric tracing task. The maximum voluntary contraction (MVC) of each muscle and %MVC (muscle contraction during a task/MVC × 100) were used as the indexes of muscle fatigue. RESULTS: The shape of the hand grip significantly reduced %MVC, which is associated with muscle fatigue. The torque of conduits and angle of the nozzle tended to reduce muscle fatigue but not significantly. Weight balance did not affect muscle fatigue. Based on these results, we made two refined models: model α (torque of conduits 0.2 kgf*cm, angle of nozzle 20 degrees, neutral balance, hand grip with a 2.9 × 2.0-cm oval section with angled finger rest), and model ß (torque of conduits 0.2 kgf*cm, angle of nozzle 20 degrees, neutral balance, hand grip with a 2.9-cm round section with a curved finger rest). The %MVC was significantly decreased with both types (p < 0.05 and p < 0.01, respectively), indicating reduction of muscle fatigue. CONCLUSIONS: The geometrically refined surgical device can improve muscle load during surgery and reduce the surgeon's physical stress, thus minimizing the risk of complications.

Water Veil Effect to Control Splashing from the Pulsed Water Jet Device: Minimizing the Potential Risk of Dissemination Using Surgical Aspirators.

OBJECTIVE: Maximum resection with minimum damage to normal structures is required for a better clinical outcome. Several efficient surgical devices such as the Cavitron ultrasonic surgical aspirator are available. Our group developed the actuator-driven pulsed water jet (ADPJ) to dissect soft tissue with vessel preservation. Although these devices are very effective for resection, tumor seeding is a potential risk. The present study investigated the control of splashing during ADPJ use. We demonstrate the effect of additional water flow around the instrument tip to veil the splashing. METHODS: Pulsed water jet was ejected from the tip of the ADPJ nozzle. Effects of ADPJ parameters such as input voltage, suction pressure, and distance between the nozzle and the target (standoff distance) on the amount of splashing were analyzed. Methylene blue solution was ejected on photo paper, gelatin brain phantom, and porcine brain harvested and subsequently immersed into physiologic saline to quantify the amount of splashing. RESULTS: High-input voltage and a long standoff distance had significant correlations with large amounts of splashing (r > 0.5; p < 0.01). However, suction pressure had no correlation (r = 0.23). Additional water flow combined with the ADPJ decreased the amount of splashing. A high-speed camera recording revealed that the additional water flow formed a water veil that prevented droplet dispersion, as confirmed with experiments using the brain phantom and porcine brain, in which the irregularity and elasticity are specific. CONCLUSIONS: The veil effect of additional water flow is important to reduce splashing during ADPJ use and can minimize the potential risk of dissemination and enhance the safety of the ADPJ.