Targeting murine small bowel and colon through selective superior mesenteric artery injection

Abstract

Administration of molecular, pharmacologic, or cellular constructs to the intestinal epithelium is limited by luminal surface mucosal barriers and ineffective intestinal delivery via systemic injection. Many murine models of intestinal disease are used in laboratory investigation today and would benefit specific modulation of the intestinal epithelium. Our aim was to determine the feasibility of a modified microsurgical approach to inject the superior mesenteric artery (SMA) and access the intestinal epithelium. We report the detailed techniques for selective injection of the SMA in a mouse. Mice were injected with methylene blue dye to grossly assess vascular distribution, fluorescent microspheres to assess biodistribution and viral vector to determine biological applicability. The procedure yielded good recovery with minimal morbidity. Tissue analysis revealed good uptake in the small intestine and colon. Biodistribution analysis demonstrated some escape from the intestine with accumulation mainly in the liver. This microsurgical procedure provides an effective and efficient method for delivery of agents to the small intestine and colon, including biological agents.

Probing Gut Participation in Parkinson’s Disease Pathology and Treatment via Stem Cell Therapy

“…In addition, pharmacological treatments only offer palliative rather than disease-modifying outcomes in PD [ 5 ]. Stem cell transplantation for PD has been shown safe and effective in laboratory studies, but with varying efficacy readouts in the clinic [ 17 ]. To this end, cell replacement and by-stander effects have been implicated as mechanisms underlying the therapeutic effects of stem cell therapy in PD and other neurological disorders [ 18 , 19 ].…”

Vasculature in the mouse colon and spatial relationships with the enteric nervous system, glia, and immune cells

“…For instance, the renal glomeruli and arterioles control both in-and out-flow (Hill et al, 2003;Murray and Paolini, 2022), and the "portal triad" in the liver and the hepatic sinusoids along the hepatocytes in the lobules return blood from the digestive tract and spleen to the liver (Gibert-Ramos et al, 2021). Compared to other visceral organs (Cao et al, 2018;Mühlfeld, 2021;Luxán and Dimmeler, 2022;Zhu et al, 2022), including the stomach and small intestine (Fu et al, 2013;Jaffey et al, 2021), the colonic vasculature is less thoroughly imaged in the different segments and layers (Ravnic et al, 2005;Ma et al, 2007;Porvasnik et al, 2010). The colon is an organ involved in fluid and electrolyte homeostasis, microbiota-gut-brain communication, and the expulsion of body waste.…”