Biology subjects

Avritscher, R.

Publications and source records attributed to Avritscher, R..

3 recordsLinked to original sources

bioRxiv2024

Transarterial Embolization Using a Liquid Embolic Enhances Tumor Necrosis to Enable Improved Efficacy Compared with a Particle Embolic in a Translational Rat Model of Hepatocellular Carcinoma

PurposeTo compare the effectiveness of transarterial embolization (TAE) using a liquid embolic (LE) to TAE using particle embolics (PE) with respect to tumor ischemia and treatment response in a translational rat model. Materials and MethodsHCC was induced in male Wistar rats using diethylnitrosamine. Rats were randomized into three treatment groups: sham transarterial embolization (TAE), TAE with LE, and TAE with PE. Tumor response to TAE was monitored via serial T2-weighted MRI scans and assessed using RECIST. Tumor necrosis and hypoxia were assessed through hematoxylin and eosin staining and pimonidazole immunohistochemistry, respectively. Statistical analyses were performed using chi-square tests, Kaplan-Meier estimates, and one-way ANOVAs, with significance set at p<0.05. ResultsTwenty-nine rats were randomized to TAE with LE (n=13), PE (n=13), or sham (n=3). TAE with LE demonstrated a significantly higher objective response rate (83%) compared to TAE with PE (28%; {chi}2 = 11.25, P=0.0008). Complete responses were observed in 50% of the LE-treated tumors versus 10% in the PE-treated group. LE treatment prolonged local progression-free survival (hazard ratio = 0.23; p=0.0085). Histological analysis, with an additional 14 rats randomized to TAE with LE (n=5), PE (n=6), or sham (n=3), showed greater necrosis and hypoxia in LE-treated tumors compared to PE. LE induced a significant reduction in viable tumor tissue (p<0.05) and increased necrotic and hypoxic tissue areas compared to PE (p<0.01). ConclusionLE significantly enhanced the therapeutic efficacy of TAE in a rat model of HCC compared to conventional PE. The results highlight LEs potential to improve ischemia and necrosis, thereby offering a promising option improving the efficacy of embolization for HCC treatment.

cancer biology↗

bioRxiv2023

Gold Nanoparticles for Monitoring of Mesenchymal Stem Cell-Loaded Bioresorbable Polymeric Wraps for Arteriovenous Fistulas

BackgroundTo address high rates of arteriovenous fistula (AVF) failure, a mesenchymal stem cell (MSC)-seeded polymeric perivascular wrap has been developed to reduce neointimal hyperplasia (NIH) and enhance AVF maturation in a rat model. However, the wraps radiolucency makes its placement and integrity difficult to monitor. PurposeIn this study, we infused gold nanoparticles (AuNPs) into the polymeric perivascular wrap to improve its radiopacity and tested the effect of infusion on the previously reported beneficial effects of the polymeric wrap on the AVF outflow vein. Materials and MethodsWe fabricated a polymeric perivascular wrap made of polycaprolactone (PCL) infused with AuNPs via electrospinning. Sprague-Dawley rat mesenchymal stem cells (MSCs) were seeded on the surface of the wraps. We then compared the effect of five AVF treatments--no perivascular wrap (i.e., control), PCL wrap, PCL+MSC wrap, PCL-Au wrap, and PCL-Au+MSC wrap--on AVF maturation in a Sprague-Dawley rat model of chronic kidney disease (n=3 per group). Statistical significance was defined as p<.05, and one-way analysis of variance was performed using GraphPad Prism software. ResultsOn micro-CT, AuNP-infused wraps demonstrated significantly higher radiopacity compared to wraps without AuNPs. On ultrasonography, wraps with and without AuNPs equally reduced the wall-to-lumen ratio of the outflow vein, a marker of vascular stenosis. On histomorphometric analysis, wraps with and without AuNPs equally reduced the neointima-to- lumen ratio of the outflow vein, a measure of NIH. On immunofluorescence analysis, representative MSC-seeded wraps demonstrated reduced neointimal staining for markers of smooth muscle cells (-SMA), inflammatory cells (CD45), and fibroblasts (vimentin) infiltration when compared to control and wraps without MSCs. ConclusionGold nanoparticle infusion allows the in vivo monitoring via micro-CT of a mesenchymal stem cell-seeded polymeric wrap over time without compromising the benefits of the wrap on arteriovenous fistula maturation. Summary StatementGold nanoparticle infusion enables in vivo monitoring via micro-CT of the placement and integrity over time of mesenchymal stem cell-seeded polymeric wrap supporting arteriovenous fistula maturation. Key ResultsO_LIGold nanoparticle (AuNP)-infused perivascular wraps demonstrated higher radiopacity on micro-CT compared with wraps without AuNPs after 8 weeks. C_LIO_LIAuNP-infused perivascular wraps equally improved the wall-to-lumen ratio of the outflow vein (a marker of vascular stenosis) when compared with wraps without AuNPs, as seen on US. C_LIO_LIAuNP-infused perivascular wraps equally reduced the neointima-to-lumen ratio of the outflow vein (a measure of neointimal hyperplasia) when compared with wraps without AuNPs, as seen on histomorphometry. C_LI

bioengineering↗

bioRxiv2022

Bioresorbable mesenchymal stem cell-loaded electrospun polymeric scaffold inhibits neointimal hyperplasia following arteriovenous fistula formation in a rat model of chronic kidney disease

In the setting of chronic kidney disease (CKD), the periadventitial injection of mesenchymal stem cells (MSCs) has shown significant potential in improving arteriovenous fistula (AVF) maturation by inhibiting neointimal hyperplasia (NIH). However, the rapid clearance of MSCs remains a challenge. Hence, we fabricated an electrospun perivascular scaffold from polycaprolactone (PCL) to support MSC attachment and allow gradual MSC elution at the outflow vein, the AVF site most prone to NIH. We performed a 5/6th nephrectomy to induce CKD in Sprague-Dawley rats, followed by direct AVF formation and perivascular scaffold application. We then compared the following groups of CKD rats: no perivascular scaffold (i.e., control), PCL scaffold, and PCL+MSC scaffold. On ultrasonography, the PCL and PCL+MSC groups showed significantly reduced wall thickness and wall-to-lumen ratio and increased luminal diameter and flow rate. Of note, the PCL+MSC group showed greater improvement in luminal diameter and flow rate compared to PCL alone. Moreover, 18F-fluorodeoxyglucose positron emission tomography showed that only PCL+MSC resulted in a significant reduction in uptake. On histology, the PCL and PCL+MSC groups showed significantly reduced neointima-to-lumen and neointima-to-media ratios and reduced neointimal CD45, -SMA, and vimentin fluorescence staining compared to the control. Although the two scaffold treatments did not differ significantly in histology, in vivo imaging suggested that the addition of MSCs promoted greater luminal expansion and blood flow and reduced the inflammatory process underlying NIH. Our results demonstrate the utility of mechanical support loaded with MSCs at the outflow vein immediately after AVF formation to support maturation by minimizing NIH.

bioengineering↗