Abstract
In the present study, we developed a sonoporation system, namely “direct sonoporation”, for transfecting the peritoneum from a defined surface area to avoid systematic side effects. Here, the transfection characteristics are explained because there is less information about direct sonoporation. Naked pDNA and nanobubbles were administered to diffusion cell attached to the visceral and parietal peritoneum from the liver and peritoneal wall surface, respectively. Then, ultrasound was irradiated. Direct sonoporation showed a higher transfection efficacy at the applied peritoneum site from the liver surface while other sites were not detected. Moreover, transgene expression was observed in the peritoneal mesothelial cells (PMCs) at the applied peritoneum site. No abnormality was observed in the inner part of the liver. Although transgene expression of the visceral peritoneum was tenfold higher than that of the parietal peritoneum, transgene expression was observed in the PMCs on both the applied peritoneum sites. These results suggest that direct sonoporation is a site-specific transfection method of the PMCs on the applied peritoneum site without transgene expression at other sites and show little toxicity in the inner tissues at the applied site via cavitation energy. This information is valuable for the development of an intraperitoneal sonoporation device for treatment of peritoneal diseases such as peritoneal fibrosis.
Highlights
The peritoneum is composed of peritoneal mesothelial cells (PMCs) and a submesothelial layer as stroma
Multi-color deep imaging analysis showed that transgene expression was observed only on the peritoneal wall surface cells as the PMCs (Figure 6c,d). These results suggest that direct sonoporation to the parietal peritoneum from the peritoneal wall surface enable site-specific transfection to the PMCs on the applied parietal peritoneum site
There is a difference in the transfection efficacy, these results suggest that direct sonoporation via the peritoneal tissue surface transfected sufficient gene to both the visceral and parietal peritoneum
Summary
The peritoneum is composed of peritoneal mesothelial cells (PMCs) and a submesothelial layer as stroma. The peritoneum is a membrane that covers peritoneal tissues (liver, stomach etc.) and plays important roles such as protecting the intraperitoneal tissues, transporting low molecular compounds, and regulating peritoneal inflammation [1]. The peritoneum is used as a peritoneal dialysis membrane for treatment of patients with end-stage renal failure. Long-term peritoneal dialysis causes peritoneal inflammation and/or peritoneal fibrosis [2,3,4]. Effective therapeutic method for peritoneal fibrosis have not been developed, and it is difficult to continue with peritoneal dialysis. It is necessary to develop a therapeutic method for treatment of peritoneal fibrosis
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