With the advent of technology to maintain intestinal epithelial stem cells in culture, there has emerged a growing interest in the use of these adult stem cells for many applications. During the period of grant support, we have developed a novel co-culture method to expand intestinal intraepithelial lymphocytes (IELs) together with intestinal epithelial cells, which allows us to investigate dynamic interaction between these two cell populations (J Gastroenterol 2016). We also assessed whether intestinal stem cells in culture are able to reconstitute normal epithelia when transplanted. To experimentally prove this, we performed transplantation experiments. Cultured epithelial stem cells obtained from the adult colon, fetal small intestine (SI), or adult SI were transplanted into the colonic lumen of recipients mice in which colonic epithelial injuries was induced. It was found that all types of cultured cells engrafted on recipients’ colons, showing their stem cell properties to regenerate normal intestinal epithelia (Nat Med 2012, Cell Stem Cell 2013, Genes Dev 2014). Interestingly, fetal small intestinal cells showed plasticity in regard to their fate to adapt to the colonic microenvironment. By contrast, small intestinal cells of adult origin did not show such plasticity and maintain their identity along the gastrointestinal tract, even after being heterotopically transplanted. These data provide the evidence that cultured intestinal stem cells of different origins could be the source for the cell therapy for various intestinal diseases in humans.