Unformatted text preview: he toxic effects of anticancer drugs on these cells frequently limit the effectiveness of chemotherapy in cancer treatment. Hematopoietic stem cell transplantation provides an approach to bypassing this toxicity, thereby allowing the use of higher drug doses to treat the patient's cancer more effectively. In this procedure, the patient is treated with high doses of chemotherapy that would normally not be tolerated because of toxic effects on the hematopoietic system (Figure 17.22). The potentially lethal damage is repaired, however, by transferring new hematopoietic stem cells (obtained either from bone marrow or peripheral blood) to the patient following completion of chemotherapy, so that a normal hematopoietic system is restored. In some cases, the stem cells are obtained from the patient prior to chemotherapy, stored, and then returned to the patient once chemotherapy is completed. However, it is important to ensure that these cells are not contaminated with cancer cells. Alternatively, the stem cells to be transplanted can be obtained from a healthy donor (usually a close relative) whose tissue type closely matches the patient. In addition to their use in cancer treatment, hematopoietic stem cell transfers are used to treat patients with diseases of the hematopoietic system, such as aplastic anemia, hemoglobin disorders, and immune deficiencies. Epithelial stem cells have also found clinical application in the form of skin grafts that are used to treat patients with burns, wounds, and ulcers. One approach to these procedures is to culture epidermal skin cells to form an epithelial sheet, which can then be transferred to the patient. Because the patient's own skin can be used for this procedure, it eliminates the potential complication of graft rejection by the immune system. The possibilities of using adult stem cells for similar replacement therapies of other diseases, including diabetes, Parkinson's disease, and muscular dystrophies, are being actively pursued. However, these clinical applications of adult stem cells are limited by the difficulties in isolating and culturing the appropriate stem cell populations. Embryonic Stem Cells and Therapeutic Cloning
While adult stem cells are difficult to isolate and culture, it is relatively straightforward to isolate and propagate the stem cells of early embryos (embryonic stem cells). These cells can be grown indefinitely as pure stem cell populations while maintaining the ability to give rise to all of the differentiated cell types of adult organisms. Consequently, there has been an enormous interest in embryonic stem cells from the standpoints of both basic science and clinical applications.
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CELL DEATH AND CELL RENEWAL 23 KEY EXPERIMENT Culture of Embryonic Stem Cells
Isolation of a Pluripotent Cell Line from Early Mouse Embryos Cultured in Medium Conditioned by Teratocarcinoma Stem Cells
Gail R. Martin University of California at San Francisco Proceedings of the National Academy of Science, USA, 1981, Volume 78, pages 76347638 The Context
The cells of early embryos are unique in their ability to proliferate and differentiate into all of the types of cells that make up the tissues and organs of adult animals. In 1970 it was found that early mouse embryos frequently developed into tumors if they were removed from the uterus and transplanted to an abnormal site. These tumors, called teratocarcinomas, contained cells that were capable of forming an array of different tissues as they grew within the animal. In addition, cells from teratocarcinomas (called embryonal carcinoma cells) could be isolated and grown in tissue culture. These cells resembled normal embryo cells and could be induced to differentiate into a variety of cell types in culture. Some embryonal carcinoma cells could also participate in normal development of a mouse if they were injected into early mouse embryos (blastocysts) that were then implanted into a foster mother. The ability of embryonal carcinoma cells to differentiate into a variety of
(A) (B) cell types and to participate in normal mouse development suggested that these tumor-derived cells might be closely related to normal embryonic stem cells. However, the events that occurred during the establishment of teratocarcinomas in mice were unknown. Gail Martin hypothesized that the embryonal carcinoma cells found in teratocarcinomas were essentially normal embryo cells that proliferated abnormally simply because, when they were removed from the uterus and transplanted to an abnormal site, they did not receive the appropriate signals to induce normal differentiation. Based on this hypothesis, she attempted to culture cells from mouse embryos with the goal of isolating normal embryonic stem cell lines. Her experiments, together with similar work by Martin Evans and Matthew Kaufman (Establishment in cultur...
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