Improved Patency of ePTFE Grafts as a Hemodialysis Access Site by Seeding Autologous Endothelial Cells Expressing Fibulin-5 and VEGF

Abstract

Small caliber synthetic vascular grafts used for dialysis access sites have high failure rates due to neointima formation and thrombosis. Seeding synthetic grafts with endothelial cells (ECs) provides a biocompatible surface that may prevent graft failure. We tested the use of ePTFE grafts seeded with autologous ECs expressing fibulin-5 and vascular endothelial growth factor (VEGF), as a dialysis access site in a porcine model. We connected the carotid arteries and jugular veins of 12 miniature pigs using 7-mm ePTFE grafts; five grafts were seeded with autologous venous ECs modified to express fibulin-5 and VEGF, and seven unseeded grafts were implanted at the same location and served as controls. At 6 months, after completion of angiography, the carotid arteries and jugular veins with the connecting grafts were excised and fixed. Autologous EC isolation and transduction and graft seeding were successful in all animals. At 3 months, 4 of 5 seeded grafts and 3 of 7 control grafts were patent. At 6 months, 4 of 5 (80%) seeded grafts and only 2 of 7 (29%) control grafts were patent. Seeding ePTFE vascular grafts with genetically modified ECs improved long term small caliber graft patency. The biosynthetic grafts offer a novel therapeutic modality for vascular access in hemodialysis.

Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM

“…Among those, 140 SAAVs in 131 proteins occurred only in NM patients (Figure 2D; Table S4), and 223 proteins in 18 MT patients had 256 SAAVs, of which 110 SAAVs in 100 proteins occurred in both NM and MT samples (Figure 2D; Table S5), and 203 SAAVs in 184 proteins only occurred in MT samples (Figure 2D; Table S6). Similarly to single nucleotide variants (SNVs), some mutations reported previously, such as those in TP53, antigen-presenting cells (APCs), vascular endothelial growth factor (VEGF), and SMAD4 were found 39, 40, 41, 42, 43. Among these, two mRNA-protein positively changed and metabolism-related proteins, FDFT1, a 47-kDa membrane-associated enzyme located at a branch point in the mevalonate pathway involved in the replication stage of the hepatitis virus C (HCV) life cycle 44 and paclitaxel sensitivity in hypopharynx cancer cell, 45 and UQCR5, a component of the ubiquinol-cytochrome c reductase complex, amplifying in primary breast cancer core biopsy samples46, 47, 48 and overexpressing in gastric cancer, 49 were found to be an occurrence of somatic alterations, which was validated with Sanger sequencing, in the 18.2% (8/44) and 9.1% (4/44) of CRC, and are specific to CLM (Figure 3A).…”

Power and Promise of Next-Generation Sequencing in Liquid Biopsies and Cancer Control

“…The detection and analysis of whole-genome sequencing (WGS), whole-exome sequencing (WES), and RNA sequencing (RNA-Seq) on T cells and tumor cells by NGS technology can obtain genome maps of tumors and immune cells, which can help to customize treatment schemes for specific characteristics of tumors and increase the possibility of success. [82][83][84] At the same time, NGS technology can be used to evaluate the changes in biomarkers of immunological checkpoint inhibitors, such as tumor mutational burden (TMB), microsatellite instability, and PD-L1 amplification and other therapeutic effects, drug resistance, and genetic mutations related to hyperprogression. 64,[85][86][87] In cancer vaccines, the immune system is stimulated to produce antibodies.…”

Targeting Colorectal Cancer Stem Cells as an Effective Treatment for Colorectal Cancer

“… 42 In the HCT116 cell line, epidermal growth factor (EGF) was also found to be essential for maintaining stem cell proliferation. 43 - 46 Inhibition of autophosphorylation of EGF receptor (EGFR1) and downstream signaling pathway protein AKT and extracellular signal-regulated kinase ERK1/2 decreases proliferation and induces apoptosis in CCSCs. 47 Conditional inactivation of the telomerase reverse transcriptase ( TERT ) gene in colonic epithelial cells of newborn mice can induce overexpression of colonic crypts in mice, causing an increase in mucosal thickness and an increase in the number of goblet cells.…”