Stem cells in gastroenterology and hepatology

Abstract

Cellular and tissue regeneration in the gastrointestinal tract and liver depends on stem cells with properties of longevity, self-renewal and multipotency. Progress in stem cell research and the identification of potential esophageal, gastric, intestinal, colonic, hepatic and pancreatic stem cells provides hope for the use of stem cells in regenerative medicine and treatments for disease. Embryonic stem cells and induced pluripotent stem cells have the potential to give rise to any cell type in the human body, but their therapeutic application remains challenging. The use of adult or tissue-restricted stem cells is emerging as another possible approach for the treatment of gastrointestinal diseases. The same self-renewal properties that allow stem cells to remain immortal and generate any tissue can occasionally make their proliferation difficult to control and make them susceptible to malignant transformation. This Review provides an overview of the different types of stem cell, focusing on tissue-restricted adult stem cells in the fields of gastroenterology and hepatology and summarizing the potential benefits and risks of using stems cells to treat gastroenterological and liver disorders.

Figure 1

Schematic illustration of the potency and differentiation status of the different stem cells and progenitor cells or differentiated tissue cells that are relevant to gastroenterology. The differentiation status of cells ranges from completely undifferentiated, totipotent cells to fully differentiated, unipotent cells. Stem cells, which range from pluripotent to multipotent, can be classified as embryonic or adult, and within the gastrointestinal tract they can be further subdivided (for example, hepatic, pancreatic and intestinal). Excluding the zygote or blastocyst, the ESC is the most potent cell and can give rise to any tissue cell of the body. Whether the rare, artificially iPSCs are identical to ESCs has yet to be defined. Adult tissue-restricted stem cells, such as gastrointestinal tissue stem cells, lack cell-specific patterns of expression but give rise to so-called progenitor cells. These, in turn, produce cellular descendants that have a more restricted lineage potential. MSCs and tissue-restricted stem cells are multipotent and both might give rise to potential gastrointestinal cancer stem cells. Abbreviations: BMDC, bone marrow-derived stem cell; ESC, embryonic stem cell; IPSC, induced pluripotent stem cell; ISC, intestinal stem cell; MSC, mesenchymal stem cell.

Figure 2

Schematic illustration of the location of putative intestinal stem cells and/or progenitor cells and their markers in the crypt of the intestine. Quiescent stem cells may be located at position +4, the more active stem cells (crypt base columnar cells [CBCs]) are located anywhere from position +1 to +4 scattered between the Paneth cells. The intestinal glands are surrounded by stromal cells (niche cells), such as myofibroblasts. Modified from Quante, M. & Wang, T. C. Physiology (Bethesda) 23, 350–359 (2008).

Figure 3

Schematic illustration of the different location and structural organization of stem cells in the gut. The a | intestine, b | esophagus and c | stomach are shown. d | Quiescent stem cells through asymmetric division probably give rise to more rapidly dividing active stem cells, which then produce progenitor cells, while losing their multipotency and ability to proliferate. All of these progeny cells have defined positions in the different organs. To maintain its function the stem cell can give rise to another stem cell at the same position (symmetric division).