The realization that cells with extensive potential for growth and differentiation occur in a variety of tissues also provides novel angles for understanding disease mechanisms. Since stem cells regulate the dynamics of normal tissues, a surprising range of disorders, including gastric atrophy, Alzheimer’s disease, and, perhaps more intuitively, various forms of cancer, can be traced to altered stem cell function. The trend toward defining stem cells primarily based on our ability to manipulate them in culture should also inspire us to devise novel models of these diseases, by analyzing genetically altered or carcinogen-treated stem cells either in vitro or in vivo after transplantation into host animals. Thus, even without improved tissue engineering or replacement, the study of stem cells may deepen our understanding of their pathogenic roles and facilitate the design of novel treatments.
This Perspective series will present many of these new aspects of stem cell biology and will show the diversity of stem cells that can be found in various nonhematopoietic tissues. The articles represent current thoughts on a broad array of stem cell types, and the topics were selected not only to draw attention to their diversity, but also to offer up for discussion to the readership at large the current controversies and challenges that face the field. As put forth in these articles, a new conceptual framework is needed for thinking about stem cells and their capacities. This framework will need to accommodate emerging findings on different classes of stem cells and should allow us to better recognize the normal and pathological roles of stem cells and to develop novel approaches for the treatment of defects and disease.
Cancer Research
Pluripotent stem cells have the ability to divide without limit and give rise to many specialized cells in an organism. There are several reasons why human pluripotent stem cells may be important to cancer research and reducing the cancer burden. First, pluripotent stem cells may be used to treat the tissue toxicity brought on by cancer therapy. Bone marrow and peripheral blood multipotent stem cells (which are more committed stem cells) are used already to restore patients' hematopoietic and immune systems after high dose chemotherapy. However, pluripotent stem cells may have greater potential for returning the complete repertoire of immune response to patients undergoing bone marrow transplantation, thus contributing to the development of other treatments such as immune/vaccine therapy. Other tissues damaged by cancer therapy also may benefit by replenishing their stem cell pools, e.g., injection of pluripotent stem cells into the heart may permanently reverse cardiomyopathy caused by certain chemotherapeutic agents, injection of pluripotent stem cells that have been differentiated into neural cells may restore brain function after cancer treatment.
A second reason why stem cells may be important to cancer research is based on the finding that cancer cells may have certain stem cell properties, specifically, the ability to renew themselves. The isolation and characterization of stem cells and in depth study of their molecular and cellular biology may help scientists understand why cancer cells survive despite very aggressive treatments. Once the cancer cell's ability to renew itself is understood, scientists can develop strategies for circumventing this property.
A third and final reason for studying stem cells lies in the field of gene therapy, where a gene that provides a missing or necessary protein is introduced into an organ for a therapeutic effect. One of the most difficult problems in gene therapy studies has been the loss of expression (or insufficient expression) following introduction of the gene into more differentiated cells. Introduction of the gene into stem cells to achieve sufficient long term expression would be a major advance. In addition, the stem cell is clearly a more versatile target cell for gene therapy, since it can be manipulated to become theoretically any tissue. A single gene transfer into a pluripotent stem cell could enable scientists to generate stem cells for blood, skin, liver, or even brain targets. Applications to cancer might include engineering replacement cells that are resistant to chemotherapeutic assault or that express antibodies against cancer targets.
Cardiovascular Research
