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Live intravital 3D imaging will clarify the spatiotemporal dynamics of intestinal stem cell regeneration

Inflammatory bowel disease (IBD) is a complex disease caused by both genetic and environmental factors. More than one million people are affected in the United States and the estimated direct healthcare cost is about 6 billion dollars per year. In the intestines of Crohn’s disease patients, only limited areas of intestines are affected. These areas are described as “skip lesions” because discontinuous lesions are scattered throughout the intestines. These lesions are often resistant to a systemic anti TNFα treatment and significantly affect the patients’ quality of life. However, little is known about how these lesions develop and are healed.

This lack of knowledge is partially because of the lack of an observational system. General histological analysis with tissue sections only provides two dimensional images at a single time point. Even if sections are taken at multiple time points, it is difficult to understand the dynamics of the intestinal stem cell regeneration because we are not seeing the same part of the intestines.

We aim to develop a live intravital 3D imaging system which enables us to see real time movements of intestinal stem cells in live animals. Recent advancements in confocal microscopy enable us to see deeper portions of the intestine to visualize the stem cells in 3 dimensions. By applying this system to reporter mice which possess labeled intestinal stem cells and have colitis, we can clarify how intestinal stem cells behave during the destruction and regeneration of intestinal epithelial cells.

Solid understanding of the spatiotemporal dynamics of intestinal stem cell regeneration should contribute to a clinical treatment for skip lesions in IBD patients who are resistant to current systemic anti-inflammatory cytokine treatment.