Impurity of Stem Cell Graft by Murine Embryonic Fibroblasts – Implications for Cell-Based Therapy of the Central Nervous System

Stem cells have been demonstrated to possess a therapeutic potential in experimental models of various central nervous system disorders, including stroke. The types of implanted cells appear to play a crucial role. Previously, groups of the stem cell network NRW implemented a feeder-based cell line within the scope of their projects, examining the implantation of stem cells after ischemic stroke and traumatic brain injury. Retrospective evaluation indicated the presence of spindle-shaped cells in several grafts implanted in injured animals, which indicated potential contamination by co-cultured feeder cells (murine embryonic fibroblasts – MEFs). Because feeder-based cell lines have been previously exposed to a justified criticism with regard to contamination by animal glycans, we aimed to evaluate the effects of stem cell/MEF co-transplantation. MEFs accounted for 5.3 ± 2.8% of all cells in the primary FACS-evaluated co-culture. Depending on the culture conditions and subsequent purification procedure, the MEF-fraction ranged from 0.9 to 9.9% of the cell suspensions in vitro. MEF survival and related formation of extracellular substances in vivo were observed after implantation into the uninjured rat brain. Impurity of the stem cell graft by MEFs interferes with translational strategies, which represents a threat to the potential recipient and may affect the graft microenvironment. The implications of these findings are critically discussed

A novel minimally invasive technique for lumbar decompression, realignment, and navigated interbody fusion

We present a novel, minimally invasive, navigation-guided approach for surgical treatment of degenerative spondylolisthesis (DS) that is a hybrid of the two most common techniques, posterior interbody fusion (PLIF) and transforaminal interbody fusion (TLIF). DS is an acquired condition with intersegmental instability of one or more lumbar motion segments. Seven patients with single level lumbar DS underwent lumbar arthrodesis utilizing the hybrid technique (HLIF) in our center. Using a standard unilateral midline approach a decompression and partial facetectomy on one side was performed, allowing for implantation of a specially designed interbody cage. Pedicle screws were placed using neuronavigation in a vertical vector on the side of the partial facetectomy and dorsolaterally (percutaneous) on the contralateral side. Patient and operative data, numeric rating scale (NRS) pain scores, core outcome measures index (COMI) and Oswestry disability index (ODI) were recorded preoperatively as well as 6 weeks, 3 months, 6 months and 1 year after surgery. All patients completed the 1 year follow-up. There was significant postoperative improvement of NRS, COMI and ODI scores at all postoperative follow-up time points (p < 0.05). The radiological assessments of realignment showed a reduction of listhesis from an average of 21.04% (standard deviation [SD] 5.1) preoperatively to 9.14% (SD 4.0) postoperatively (p < 0.001). The average blood loss was 492 ml. Post-procedure CT scans demonstrated correct implant placement in all but one patient who required a revision of a single pedicle screw. HLIF allows thorough decompression as well as realignment and interbody fusion for patients with DS and may help reduce tissue trauma in comparison to other minimally invasive lumbar fusion techniques. (C) 2015 Elsevier Ltd. All rights reserved

First clinical results of minimally invasive vector lumbar interbody fusion (MIS-VLIF) in spondylodiscitis and concomitant osteoporosis: a technical note

First description of MIS-VLIF, a minimally invasive lumbar stabilization, to evaluate its safety and feasibility in patients suffering from weak bony conditions (lumbar spondylodiscitis and/or osteoporosis). After informed consent, 12 patients suffering from lumbar spondylodiscitis underwent single level MIS-VLIF. Eight of them had a manifest osteoporosis, either. Pre- and postoperative clinical status was documented using numeric rating scale (NRS) for leg and back pain. In all cases, the optimal height for the cage was preoperatively determined using software-based range of motion and sagittal balance analysis. CT scans were obtained to evaluate correct placement of the construct and to verify fusion after 6 months. Since 2013, 12 patients with lumbar pyogenic spondylodiscitis underwent MIS-VLIF. Mean surgery time was 169 +/- 28 min and average blood loss was less than 400 ml. Postoperative CT scans showed correct placement of the implants. Eleven patients showed considerable postoperative improvement in clinical scores. In one patient, we observed screw loosening. After documented bony fusion in the CT scan, the fixation system was removed in two cases to achieve lower material load. The load-bearing trajectories (vectors) of MIS-VLIF are different from those of conventional coaxial pedicle screw implantation. The dorsally converging construct combines the heads of the dorsoventral pedicle screws with laminar pedicle screws following cortical bone structures within a small approach. In case of lumbar spondylodiscitis and/or osteoporosis, MIS-VLIF relies on cortical bony structures for all screw vectors and the construct does not depend on conventional coaxial pedicle screws in the presence of inflamed, weak, cancellous or osteoporotic bone. MIS-VLIF allows full 360 degrees lumbar fusion including cage implantation via a small, unilateral dorsal midline approach

Predictive modeling and in vivo assessment of cerebral blood flow in the management of complex cerebral aneurysms

Cerebral aneurysms are weakened blood vessel dilatations that can result in spontaneous, devastating hemorrhage events. Aneurysm treatment aims to reduce hemorrhage events, and strategies for complex aneurysms often require surgical bypass or endovascular stenting for blood flow diversion. Interventions that divert blood flow from their normal circulation patterns have the potential to result in unintentional ischemia. Recent developments in computational modeling and in vivo assessment of hemodynamics for cerebral aneurysm treatment have entered into clinical practice. Herein, we review how these techniques are currently utilized to improve risk stratification and treatment planning

Effects of Preoperative Simulation on Minimally Invasive Hybrid Lumbar Interbody Fusion

OBJECTIVE: The main focus of this study was to evaluate how preoperative simulation affects the surgical work flow, radiation exposure, and outcome of minimally invasive hybrid lumbar interbody fusion (MIS-HLIF). METHODS: A total of 132 patients who underwent single-level MIS-HLIF were enrolled in a cohort study design. Dose area product was analyzed in addition to surgical data. Once preoperative simulation was established, 66 cases (SIM cohort) were compared with 66 patients who had previously undergone MIS-HLIF without preoperative simulation (NO-SIM cohort). - RESULTS: Dose area product was reduced considerably in the SIM cohort (320 cGy.cm(2) NO-SIM cohort: 470 cGy.cm(2); P < 0.01). Surgical time was shorter for the SIM cohort (155 minutes; NO-SIM cohort, 182 minutes; P < 0.05). SIM cohort had a better outcome in Numeric Rating Scale back at 6 months follow-up compared with the NO-SIM cohort (P < 0.05). CONCLUSIONS: Preoperative simulation reduced radiation exposure and resulted in less back pain at the 6 months follow-up time point. Preoperative simulation provided guidance in determining the correct cage height. Outcome controls enabled the surgeon to improve the procedure and the software algorithm

Bi-specific molecule against EGFR and death receptors simultaneously targets proliferation and death pathways in tumors

Developing therapeutics that target multiple receptor signaling pathways in tumors is critical as therapies targeting single specific biomarker/pathway have shown limited efficacy in patients with cancer. In this study, we extensively characterized a bi-functional molecule comprising of epidermal growth factor receptor (EGFR) targeted nanobody (ENb) and death receptor (DR) targeted ligand TRAIL (ENb-TRAIL). We show that ENb-TRAIL has therapeutic efficacy in tumor cells from different cancer types which do not respond to either EGFR antagonist or DR agonist monotherapies. Utilizing pharmacological inhibition, genetic loss of function and FRET studies, we show that ENb-TRAIL blocks EGFR signalling via the binding of ENb to EGFR which in turn induces DR5 clustering at the plasma membrane and thereby primes tumor cells to caspase-mediated apoptosis. In vivo, using a clinically relevant orthotopic resection model of primary glioblastoma and engineered stem cells (SC) expressing ENb-TRAIL, we show that the treatment with synthetic extracellular matrix (sECM) encapsulated SC-ENb-TRAIL alleviates tumor burden and significantly increases survival. This study is the first to report novel mechanistic insights into simultaneous targeting of receptor-mediated proliferation and cell death signaling pathways in different tumor types and presents a promising approach for translation into the clinical setting

Endoscopic and Microscopic Segmental Decompression via Translaminar Crossover Spinal Approach in Elderly Patients

OBJECTIVE: For effective minimally invasive lumbar decompression, we changed the routine of segmental decompression. Using a high-speed drill or an ultrasound knife, we created a working channel, starting at the base of the spinous process of the upper vertebra slightly above the disc level, to target and decompress the contralateral recess, and termed it the translaminar crossover decompression (TCD). We evaluated the feasibility and compared the outcomes of a navigation-guided endoscopic translaminar crossover approach for segmental decompression (eTCD) in elderly patients with microscopic decompression using the same approach (mTCD). METHODS: A total of 740 elderly patients were enrolled in a prospective cohort study. Of the 740 patients, 297, who had undergone mTCD, and 253, who had undergone eTCD, completed a 1-year follow-up visit. In addition to the surgical data, numerical rating scales (NRSs) for back and leg pain, the Core Outcome Measures Index and Oswestry Disability Index were recorded preoperatively and 3, 6, and 12 months after surgery. The MacNab criteria were supplemented by qualitative assessment of the patients' postoperative pain-free walking distance. RESULTS: A comparison of the preoperative and postoperative clinical scores showed significant improvement after TCD in both cohorts (P < 0.01): Oswestry Disability Index, from 50.3% +/- 12.6% to 15.5% +/- 7.43%; NRS (back), from 6.9 +/- 1.9 to 2.5 +/- 1.3; NRS (leg), from 8.0 +/- 0.85 to 1.6 +/- 0.33; Core Outcome Measures Index (back), from 7.8 +/- 2.0 to 2.7 +/- 1.5. No statistically significant differences were found in the outcomes between the 2 cohorts. CONCLUSIONS: TCD inherently eliminated central stenosis and facilitated decompression of both recesses via mutual undercutting, with preservation of facet joint integrity

Prospective surgical solutions in degenerative spine: spinal simulation for optimal choice of implant and targeted device development

Objectives: The most important goal of surgical treatment for spinal degeneration, in addition to eliminating the underlying pathology, is to preserve the biomechanically relevant structures. If degeneration destroys biomechanics, the single segment must either be surgically stabilized or functionally replaced by prosthetic restoration. This study examines how software-based presurgical simulation affects device selection and device development. Methods: Based on videofluoroscopic motion recordings and pixel-precise processing of the segmental motion patterns, a software-based surrogate functional model was validated. It characterizes the individual movement of spinal segments relative to corresponding cervical or lumbar spine sections. The single segment-based motion of cervical or lumbar spine of individual patients can be simulated, if size-calibrated functional X-rays of the relevant spine section are available. The software plug-in biokinemetric triangle has been then integrated into this software to perform comparative segmental motion analyses before and after treatment in two cervical device studies: the correlation of implant-induced changes in the movement geometry and patient-related outcome was examined to investigate, whether this surrogate model could provide a guideline for implant selection and future implant development. Results: For its validation in 253 randomly selected patients requiring single-level cervical (n=122) or lumbar (n=131) implant-supported restoration, the biokinemetric triangle provided significant pattern recognition in comparable investigations (p<0.05) and the software detected device-specific changes after implant-treatment (p<0.01). Subsequently, 104 patients, who underwent cervical discectomy, showed a correlation of the neck disability index with implant-specific changes in their segmental movement geometry: the preoperative simulation supported the best choice of surgical implants, since the best outcome resulted from restricting the extent of the movement of adjacent segments influenced by the technical mechanism of the respective device (p<0.05). Conclusions: The implant restoration resulted in best outcome which modified intersegmental communication in a way that the segments adjacent to the implanted segment undergo less change in their own movement geometry. Based on our software-surrogate, individualized devices could be created that slow down further degeneration of adjacent segments by influencing the intersegmental communication of the motion segments