rada16-i and Fibrosis

Circumferential endoscopic submucosal dissection (ESD) allows to treat large esophageal superficial neoplasms, however with a high occurrence of severe esophageal strictures. In a previous work, we demonstrated that the application of a prototype of self-assembling peptide (SAP) matrix on esophageal wounds after a circumferential-ESD delayed the onset of esophageal stricture in a porcine model. The aim of this work was to consolidate these results using the commercialized version of this SAP matrix currently used as a hemostatic agent.. Eleven pigs underwent a 5 cm-long circumferential esophageal ESD under general anesthesia. Five pigs were used as a control group and six were treated with the SAP. In the experimental group, 3.5 mL of the SAP matrix were immediately applied on the ESD wound. Stricture rates and esophageal diameter were assessed at day 14 by endoscopy and esophagram, followed by necropsy and histological measurements of inflammation and fibrosis in the esophageal wall.. At day 14, two animals in the treated group had an esophageal stricture without any symptom, while all animals in the control group had regurgitations and an esophageal stricture (33 vs. 100%, p = 0.045). In the treated group, the mean esophageal diameter at day 14 was 9.5 ± 1 mm vs. 4 ± 0.6 mm in the control group (p = 0.004). Histologically, the neoepithelium was longer in the SAP treated group vs. the control (3075 μm vs. 1155μm, p = 0.014). On immunohistochemistry, the expression of alpha smooth muscle actin was lower in the treated vs. control group.. Apposition of a self-assembling peptide matrix immediately after a circumferential esophageal ESD reduced by 67% the occurrence of a stricture at day 14, by promoting reepithelialization of the resected area.

Topics: Animals; Endoscopic Mucosal Resection; Esophageal Mucosa; Esophageal Stenosis; Esophagoscopy; Esophagus; Female; Fibrosis; Hemostatics; Male; Models, Animal; Peptides; Postoperative Complications; Re-Epithelialization; Swine

Progress in stem cell transplantation for the treatment of myocardial infarction is hampered by the poor retention and survival of the implanted cells. To enhance cell survival and differentiation and thereby improve the efficiency of stem cell therapy, we constructed a novel self-assembling peptide by attaching an RGDSP cell-adhesion motif to the self-assembling peptide RADA16. c-kit(pos)/Nkx2.5(low)/GATA4(low) marrow-derived cardiac stem cells (MCSCs), which have a specific potential to differentiate into cardiomyocytes, were isolated from rat bone marrow. The cytoprotective effects of RGDSP scaffolds were assessed by exposure of MCSCs to anoxia in vitro. The efficacy of transplanting MCSCs in RGDSP scaffolds was evaluated in a female rat MI model. The designer self-assembling peptide self-assembled into RGDSP nanofiber scaffolds under physiological conditions. RGDSP scaffolds were beneficial for the growth of MCSCs and protected them from apoptosis and necrosis caused by anoxia. In a rat MI model, cardiac function was improved and collagen deposition was markedly reduced in the group receiving MCSCs in RGDSP scaffolds compared with groups receiving MCSCs alone, RGDSP scaffolds alone or MCSCs in RADA16 scaffolds. There were more surviving MCSCs in the group receiving MCSCs in RGDSP scaffolds than in the groups receiving MCSCs alone or MCSCs in RADA16 scaffolds. Most of the Y chromosome-positive cells expressed cardiac troponin T and connexin43 (Cx-43). These results suggest that RGDSP scaffolds provide a suitable microenvironment for the survival and differentiation of MCSCs. RGDSP scaffolds enhanced the efficacy of MCSC transplantation to repair myocardium and improve cardiac function.

Topics: Animals; Bone Marrow Cells; Bone Marrow Transplantation; Cell Culture Techniques; Cell Differentiation; Cell Survival; Fibrosis; Male; Myocardial Contraction; Myocardial Infarction; Myocytes, Cardiac; Nanofibers; Oligopeptides; Peptides; Rats; Rats, Sprague-Dawley; Stem Cell Transplantation; Ventricular Function, Left