Decellularized Matrix from Tumorigenic Human Mesenchymal Stem Cells Promotes Neovascularization with Galectin-1 Dependent Endothelial Interaction

BACKGROUND: Acquisition of a blood supply is fundamental for extensive tumor growth. We recently described vascular heterogeneity in tumours derived from cell clones of a human mesenchymal stem cell (hMSC) strain (hMSC-TERT20) immortalized by retroviral vector mediated human telomerase (hTERT) gene expression. Histological analysis showed that cells of the most vascularized tumorigenic clone, -BD11 had a pericyte-like alpha smooth muscle actin (ASMA+) and CD146+ positive phenotype. Upon serum withdrawal in culture, -BD11 cells formed cord-like structures mimicking capillary morphogenesis. In contrast, cells of the poorly tumorigenic clone, -BC8 did not stain for ASMA, tumours were less vascularized and serum withdrawal in culture led to cell death. By exploring the heterogeneity in hMSC-TERT20 clones we aimed to understand molecular mechanisms by which mesenchymal stem cells may promote neovascularization. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative qRT-PCR analysis revealed similar mRNA levels for genes encoding the angiogenic cytokines VEGF and Angiopoietin-1 in both clones. However, clone-BD11 produced a denser extracellular matrix that supported stable ex vivo capillary morphogenesis of human endothelial cells and promoted in vivo neovascularization. Proteomic characterization of the -BD11 decellularized matrix identified 50 extracellular angiogenic proteins, including galectin-1. siRNA knock down of galectin-1 expression abrogated the ex vivo interaction between decellularized -BD11 matrix and endothelial cells. More stable shRNA knock down of galectin-1 expression did not prevent -BD11 tumorigenesis, but greatly reduced endothelial migration into -BD11 cell xenografts. CONCLUSIONS: Decellularized hMSC matrix had significant angiogenic potential with at least 50 angiogenic cell surface and extracellular proteins, implicated in attracting endothelial cells, their adhesion and activation to form tubular structures. hMSC -BD11 surface galectin-1 expression was required to bring about matrix-endothelial interactions and for xenografted hMSC -BD11 cells to optimally recruit host vasculature

ICAR: endoscopic skull‐base surgery

n/

Risk Factors for Postoperative Urinary Retention After Endoscopic Hernia Repair: Age and Unilateral Operation make the Difference

BACKGROUND: Postoperative urinary retention (POUR) is a common complication after inguinal hernia repair that may result in catheter-related infections or injuries, longer hospital stays, and thus, higher overall costs. Our aim was to assess the incidence of POUR after endoscopic total extraperitoneal (TEP) inguinal hernia repair and identify its risk factors. METHODS: We retrospectively analyzed all data that were included in a prospective Hernia Database for patients undergoing a TEP inguinal hernia repair at our institution between July 2012 and May 2018. POUR was defined as the inability to urinate spontaneously after surgery, thus requiring a bladder catheter. RESULTS: Data from 1570 patients were included. Sixty-five patients developed POUR, which was an incidence of 4.1%. In the univariate analysis, patients over 50 years of age (1.6% vs. 5.5%), patients with higher American Society of Anesthesiologists (ASA) score (ASA-1 2.7% vs. ASA-3 12.5%), previous prostate surgery (3.9% vs. 10.9%), unilateral operation (1.9% vs. 6.0%), and intraoperative drain placement (2.1% vs. 4.9%) developed POUR more often than younger patients. After multivariate adjustment, advanced age and unilateral surgery remained risk factors for POUR. CONCLUSION: Advanced age and unilateral inguinal hernia repair, possibly due to a lack of catheterization, were risk factors for POUR. Due to increasing outpatient inguinal hernia repairs worldwide, it is imperative to identify patients who are at risk of POUR to apply prophylactic measures and reduce readmission, and thus, reduce health-care costs