Screening for radiation protectors using small intestinal organoids

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NCI	CELLBIO-3

Authors

• S. I. Chung
• D.E. Citrin

Abstract

Radiation therapy is commonly employed to treat cancer. However total body or abdominal irradiation can damage the intestinal epithelium resulting in the loss of crypts and shortening of villi. These radiation-induced gastrointestinal toxicities can manifest as malabsorption of nutrients, fluid and electrolyte loss, and sepsis. Such toxicities can affect patient quality of life and even cause death if the intestinal mucosal barrier is not repaired. To better understand the biological causes underlying gastrointestinal injury, we are isolating single crypts from C57BL/6NCr mice, culturing small intestinal organoids, and irradiating them with a single fraction of 0,2,4,6, and 8Gy. Irradiation leads to a dose-dependent decrease in organoid-forming efficiency of crypts cells and delay in budding. Based on our observations, intestinal organoids are a promising model to characterize the radioresponses of the cells types found in the intestine including enterocytes, enteroendocrine, goblet, Paneth cells and crypt base columnar stem cells. In addition, we will use the organoids to screen for radiation protectors in vitro and then validate potential candidates in mice. The goal is to apply our finding in developing a strategy to prevent and/or mitigate radiation induced intestinal injury.

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