| | |
Asymmetric division refers to cell replication in which one daughter cell enters a differentiation pathway and gives rise to mature cells, whereas the other remains undifferentiated and retains its self-renewal capacity. By contrast, in symmetric division, both daughter cells retain self renewal capacity. Such divisions are seen early in embryogenesis (when stem cell populations are expanding) and under conditions of stress, such as in the bone marrow following chemotherapy. #352 | | |
Although there is a tendency in the scientific literature to partition stem cells into several different subsets, funda- mentally there are only two varieties: #353 | | |
| | |
Embryonic stem cells (ES cells) are the most undifferenti- ated. They are present in the inner cell mass of the blastocyst, have virtually limitless cell renewal capacity, and can give rise to every cell in the body; they are thus said to be totipotent (Fig. 1.20). ES cells can be main- tained for extended periods without differentiating; thereafter, appropriate culture conditions allow them to form specialized cells of all three germ cell layers, including neurons, cardiac muscle, liver cells, and pan- #355 | | |
| | |
| | |
Tissue stem cells (also called adult stem cells) are found in intimate association with the differentiated cells of a given tissue. They are normally protected within spe- cialized tissue microenvironments called stem cell niches. Such niches have been demonstrated in many organs, most notably the bone marrow, where hematopoietic stem cells congregate in a perivascular niche. Other niches for stem cells include the bulge region of hair follicles; the limbus of the cornea; the crypts of the gut; the canals of Hering in the liver; and the subventricular zone in the brain. Soluble factors and other cells within the niches keep the stem cells quiescent until there is a need for expansion and differentiation of the precursor pool (Fig. 1.21). #358 | | |
Adult stem cells have a limited repertoire of differ- entiated cells that they can generate. Thus, although adult stem cells can maintain tissues with high (e.g., skin and gastrointestinal tract) or low (e.g., endothe- lium) cell turnover, the adult stem cells in any given tissue can usually only produce cells that are normal constituents of that tissue. #359 | | |
Hematopoietic stem cells are the most extensively studied; they continuously replenish all the cellular ele- ments of the blood as they are consumed. They can be isolated directly from bone marrow, as well as from the peripheral blood after administration of certain colony stimulating factors (CSF) that induce their release from bone marrow niches. Although rare, hematopoietic stem cells can be purified to virtual homogeneity based on cell surface markers. Clinically, these stem cells can be used to repopulate marrows depleted after chemotherapy (e.g., for leukemia), or to provide normal precursors to correct various blood cell defects (e.g., sickle cell disease; see Chapter 12). #360 | | |
Besides hematopoietic stem cells, the bone marrow (and notably, other tissues such as fat) also contains a popula- tion of mesenchymal stem cells. These are multipotent cells that can differentiate into a variety of stromal cells includ- ing chondrocytes (cartilage), osteocytes (bone), adipocytes (fat), and myocytes (muscle). Because these cells can be expanded to large numbers, they represent a potential means of manufacturing the stromal scaffolding needed for tissue regeneration. #361 | | |
Regenerative Medicine #362 | | |
The ability to identify, isolate, expand, and transplant #363 | | |
stem cells has given birth to the new field of regenerative medicine. Theoretically, the differentiated progeny of ES or adult stem cells can be used to repopulate damaged tissues or to construct entire organs for replacement. In particular, there is considerable excitement about the ther- apeutic opportunities for restoring damaged tissues that have low intrinsic regenerative capacity, such as myocar- dium after a myocardial infarct or neurons after a stroke. Unfortunately, despite an improving ability to purify and expand stem cell populations, much of the initial enthusi- asm has been tempered by difficulties encountered in introducing and functionally integrating the replacement cells into sites of damage. #364 | | |
More recently it has been possible to generate pluripo- tential cells, resembling ES cells, that are derived from the patient into whom they will be implanted. To accomplish this, a handful of genes have been identified whose prod- ucts can—remarkably—reprogram somatic cells to achieve the “stem-ness” of ES cells. When such genes are intro- duced into fully differentiated cells (e.g., fibroblasts), induced pluripotent stem cells (iPS cells) are generated (Fig. 1.22), albeit at low frequency. Because these cells are derived from the patient, their differentiated progeny (e.g., insulin-secreting β-cells in a patient with diabetes) can be engrafted without eliciting an immunologically mediated rejection reaction that would occur if the differentiated cells were derived from ES cells obtained from another donor. #365 | | |
| | |
This survey of selected topics in cell biology serves as a basis for our later discussions of pathology, and we will refer back to it throughout the book. Students should, however, remember that this summary is intentionally brief, and more information about some of the fascinating topics reviewed here can be readily found in textbooks devoted to cell and molecular biology. #367 | | |
