N. Huynh1, J. D. Rouch1, G. Dubrovsky1, A. Scott1, M. G. Martin2, S. Shekherdimian1, J. Dunn1 1University Of California – Los Angeles,Division Of Pediatric Surgery, Department Of Surgery, David Geffen School Of Medicine,Los Angeles, CA, USA 2University Of California – Los Angeles,Division Of Gastroenterology And Nutrition, Department Of Pediatrics, David Geffen School Of Medicine,Los Angeles, CA, USA
Introduction:
Distraction enterogenesis (DE) has been explored as a novel treatment in patients with short bowel syndrome (SBS). Self-expanding springs have been shown to lengthen intestines in animal models. Evidence of epithelial cellular proliferation in lengthened segments is a marker for successful intestinal growth. In this study, we evaluate stem cell growth in intestinal crypts after spring-mediated intestinal lengthening in a murine model.
Methods:
A 10 mm compressed nitinol spring was placed in a 5 mm isolated intestinal segment in mice. A non-compressed nitinol spring placed in a 5 mm isolated intestinal segment served as a control. After 1 to 2 weeks, intestinal segments were examined for size, histological analysis, and stem cell proliferation in intestinal crypts using immunofluorescence for OLFM4 and PCR for mRNA expression of Lgr5.
Results:
Intestinal segments lengthened from 5 to 9.3 ± 1.0 mm, whereas control segments lengthened from 5 to 6.0 ± 0.5 mm (p<0.01). OLFM4 immunostaining showed increased stem cell compartment growth in lengthened and control segments in comparison to normal intestine (Figure), 50.0 ± 9.4 µm and 63.1 ± 15.2 µm? versus 26.4 ± 9.6 µm (p<0.01), respectively. Lgr5 expression was increased in lengthened and control segments in comparison to normal intestine by 9-fold and 10-fold, respectively. Histologically, lengthened and control segments had increased smooth muscle thickness and crypt depth in comparison to normal small intestine.
Conclusion:
Spring-mediated DE in a mouse model led to a significant increase in intestinal length and stem cell expansion in intestinal crypts. Although control segments did not significantly lengthen, the obstruction from intestinal isolation led to an increase in stem cell proliferation. This model can be used to study factors that optimize DE and further suggests that spring-mediated intestinal lengthening is a promising treatment for SBS.