Adult Stem Cells
By Gerald Udolph, CMM Introduction and background Adult stem cells are capable of self-renewal as well as differentiation into progenitors and differentiated cell types, a characteristic shared with embryonic stem cells. Generally, adult stem cells are regarded as multipotent with a potential to give rise to most cell types within a given tissue whereas embryonic stem cells are characterized as pluripotent producing almost all cell types of the body. Embryonic stem cells are derived from the inner cell mass of the early blastocyst, however, the origin of adult stem cells is less clear and it is largely unknown when and how a particular adult stem cell type arises during development. The functions of adult stem cells are mainly twofold: they are involved in constructing particular tissue types and organs during development and also play a major role in homeostasis of mature tissues by replacing lost or damaged cells. Therefore they contribute to keeping total cell numbers constant over time and the particular organ in a functional state. Thus, one major biological role of adult stem cells is regenerative and reconstructive in nature. A major advantage of adult stem cells is that they exist and persist throughout the life span of organisms and therefore can be studied in their natural environment from where they can also be isolated and scrutinized in vitro. Most of the known adult stem cell types reside in specialized compartments called stem cell niches. The niche is a natural environment or cellular neighborhood that functions in the maintenance of stem cell state as well as generating transiently amplifying progenitor cells by tightly controlled mechanisms via cell-cell communication. The niche furthermore provides cues for a regulated exit of progenitors as well as differentiated cell types from the niche, thus serving a role as an organ specific nursery for specialized cell types
The list of adult stem cell niches is long and constantly growing. Stem cells reside in the bone marrow and cord blood (mesenchymal stem cells), brain (neural stem cells), skin (skin stem cells), and intestines (crypt stem cells) as well as hair follicles, just to name a few of the identified and characterized niches. It is thought that each stem cell residing in a particular niche will be primed to give rise to cell types of only that particular niche type thereby limiting the differentiation potential of the stem cell. A number of reports, however, indicate that adult stem cells might have the potency to give rise to tissues and cell types other than that of the niche of origin, although this concept of transdifferentiation / stem cell plasticity is still discussed controversially at the moment. Irrespective of this ongoing debate, adult stem cells give rise to multiple cell types of a particular germ layer, organ, or tissue type they are residing in. These multipotent features qualify them as possible candidates for tissue and cell replacement strategies for many human diseases. Moreover, adult stem cells can be harvested from a patients' own (autologous) body avoiding problems of tissue rejection with non-self (allogenic) cells from unrelated donors. Furthermore, particularly hematopoietic stem cells isolated from bone marrow, peripheral blood and cord blood are already successfully used in clinical settings for many years mainly, but not exclusively, for the treatment of blood related malignancies. Based on the precedence of existing clinical applications of adult stem cells, it is likely that alternative treatment options using different adult stem cell types can be more readily translated into novel clinical strategies for other than hematopoietic diseases. Further reading:
NIH Report on Stem Cells: Verfaillie, CM (2002): Adult stem cells: assessing the case for pluripotency. Trends Cell Biol 12, 502-508. Prockop et al., (2003): One strategy for cell and gene therapy: Harnessing the power of adult stem cells to repair tissues. PNAS 100, Suppl.1, 11917-11923. Spradling et al., (2001). Stem cells find their niche. Nature 414, 98-104. Upcoming articles: Mesenchymal stem cells Skin stem cells Clinical applications of stem cells |
