The Intestinal Stem Cell Niche: Generation and Utilization of Intestinal Organoids

In cell biology, the stem cell niche is the dynamic microenvironment in which stem cells reside and receive signals that determine their behavior and fate. The stem cell niche has largely been a theoretical construct due to the difficulty in identifying and manipulating individual stem cells and their surroundings. Recent technical advances have made it possible to characterize the niches that maintain and control stem cell activity in several organs, including the small intestine. Although the small intestine has a relatively simple architecture, it has an extraordinary capacity for fast self-renewal. Thus, the organ is a unique model for studying intestinal stem cells (ISCs) and their niche. The intestinal epithelium maintains the intestine, enabling it to perform its absorption, secretion, and barrier functions. ISCs reside at the base of crypts adjacent to Paneth cells. In vivo, ISCs are surrounded by the microenvironment that makes up the niche, which provides a variety of stimuli that determine the fate of the cells. Research on stem cell niches is beginning to deepen our understanding of ISC regulation at the cellular and molecular levels and is expected to provide insights that can be applied to ISC therapy. Intestinal organoids originate from a group of crypt base ISCs. These organoids possess a three-dimensional (3D) cell structure made up of the lumen facing inward. Therefore, 3D intestinal organoids are often digested and seeded in a two-dimensional (2D) manner to form confluent organoid monolayers. Here, we not only review our current understanding of ISC niches with a focus on systems that are well-characterized at the cellular and mechanistic levels, but we also summarize the current applications of intestinal organoids.