Stem cell biology is a rapidly expanding field that explores the characteristics and possible clinical applications of a variety of stem cells that serve as the progenitors of more differentiated cell types. In addition to potential therapeutic applications (Chap. 90e), patient-derived stem cells can also be used as disease models and as a means of testing drug efficacy. Stem cells and their niche are a major focus of medical research because they play central roles in tissue and organ homeostasis and repair, which are important aspects of aging and disease.
IDENTIFICATION, ISOLATION, AND DERIVATION OF STEM CELLS
The definition of stem cells remains elusive. Stem cells were originally postulated as unspecified or undifferentiated cells that provide a source of renewal of skin, intestine, and blood cells throughout life. These resident stem cells have been identified in a variety of organs (e.g., epithelia of the skin and digestive system, bone marrow, blood vessels, brain, skeletal muscle, liver, testis, and pancreas) based on their specific locations, morphology, and biochemical markers.
Unequivocal identification of stem cells requires their separation and purification, usually based on a combination of specific cell-surface markers. These isolated stem cells (e.g., hematopoietic stem [HS] cells) can be studied in detail and used in clinical applications, such as bone marrow transplantation (Chap. 89e). However, the lack of specific cell-surface markers for other types of stem cells has made it difficult to isolate them in large quantities. This challenge has been partially addressed in animal models by genetically marking different cell types with green-fluorescent protein driven by cell-specific promoters. Alternatively, putative stem cells have been isolated from a variety of tissues as side population (SP) cells using fluorescence-activated cell sorting after staining with the Hoechst 33342 dye.
It is desirable to culture and expand stem cells in vitro to obtain a sufficient quantity for analysis and potential therapeutic use. Although the derivation of stem cells in vitro has been a major obstacle in stem cell biology, the number and types of cultured stem cells have increased progressively (Table 88-1). Cultured stem cells derived from resident stem cells are often called adult stem cells or somatic stem cells to distinguish them from embryonic stem (ES) and embryonic germ (EG) cells. However, considering the existence of embryo-derived, tissue-specific stem cells (e.g., trophoblast stem [TS] cells) and the possible derivation of similar cells from an embryo/fetus (e.g., neural stem [NS] cells), it is more appropriate to use the term, tissue stem cells.
TABLE 88-1Examples of Cultured Stem Cells