The discovery of the structure and function of DNA is indisputably one of the most important scientific innovations of the 20th century. DNA is the foundation upon which modern genetics was established and has dictated the course of modern medicine over the past 50 years. Today, many believe a new exemplar is emerging that has the potential to influence the life sciences with equal magnitude – the stem cell. The idea of a stem cell dates to the 1960s experiments of Till and McCulloch and Gordon Pierce. Pierce discovered that tumorigenicity correlates with cells that have pluripotent capabilities. Teratocarcinomas (malignant tumors) produce two cell lines: C-cells that are tumorigenic and E-cells that are not. It was thus concluded that C-cells are undifferentiated cells that could give rise to both cell types and perpetuate tumor growth. The possibility of a stem cell system such as this has formed the foundation for modern stem cell research and is currently being investigated in embryonic and adult cell lines.
By definition, stem cells are cells that individually or as a population can produce differentiated progeny and reproduce themselves (Slack 1991). More specifically, they can divide without limit, are not terminally differentiated, can be either unipotent , pluripotent, or totipotent , and upon division, daughter cells can either become another stem cell or begin a process of terminal differentiation. In this article I will explore the similarities and differences between two stem cell types, adult and embryonic, both of which are being aggressively investigated for their potentially invaluable medical implications. In addition to their contributions to science, stem cells, particularly embryonic, are the focus of a public debate surrounding the ethics of research that could potentially destroy a human life. For this reason, the delineation of these cell types and elucidation of the prospects and problems associated with this research is exceedingly important.
Embryonic Stem Cells
Embryonic stem cells are those that are experimentally derived from very early embryos and have the potential to generate most somatic (i.e. non-germ) cell types (a.k.a. they are pluripotent). They are found in the inner cell mass of the blastocyst during embryonic development. The Evans, Kaufman and Martin experiments of 1981 helped to establish that ES cells can be isolated directly in culture and preserved in vitro for some time (ES cells express the transcription factor Oct-4, which activates or inhibits a number of target genes, allowing the cells to remain in a proliferative, non-differentiating state until they are induced to do so. ES cells lack the G1 checkpoint in the cell cycle and spend most of their time in the S phase, synthesizing DNA. Thus, they require no additional stimulus to initiate DNA replication (NIH 2001)). Although pluripotent cell lines have been determined for a number of different mammals including mice, pigs, cows, monkeys and humans, they have only been positively identified as embryonic stem cells in mice. This is because mice are the only mammals to show that their pluripotent cells are reproducible through germ line transmission. However, despite solid evidence, the ES cell system is widely accepted to encompasses the greater animal kingdom.
Because ES cells are the unspecialized progenitors for the adult cellular organism, their experimental and therapeutic applications are immense. If only we could master the specialization and implantation process of ES cells, their high degree of plasticity would enable us to generate any variety of body tissue in vitro or in vivo. In addition, we could virtually maintain an endless supply because they are both clonogenic – that is a single ES cell can give rise to a colony of genetically identical cells, and they have high levels of telomerase that allow them to repeatedly self-renew. However, the issue of immunosuppression resulting from the implantation of foreign cells would first have to be overcome before we could accomplish this feat.
Adult Stem Cells
Adult stem cells comprise many different types of cells – exactly which ones and how many, however, is ardently contested. They are rare and difficult to recognize, yet have been identified in many mature tissues in the body. To date, there is excellent evidence for adult stem cells in the blood, the nervous system, the intestine, and the skin, while many other tissues are currently being investigated.
Adult stem cells differ from ES cells in a variety of ways. First of all, they are not known to exist for all cell types, thus decreasing their versatility for research and therapy. They also do not grow well (or at all) in vitro, which presents a serious hindrance to research. Additionally, adult stem cells have a reduced potential for growth. This is because they are cells taken from adult organisms, which have already spent a portion of their telomeric extremities that are necessary for self-renewal.
Adult stem cells, however, are not completely subordinate to ES cells in terms of clinical and laboratory utility. Although adult stem cells harvested from adult organisms are problematic in one sense, they are beneficial in another. If the problem of culturing cells in vitro cold be overcome, adult stem cells would possess a great advantage over ES cells. They would not have the problem of being rejected upon re-implantation into the donor body (that is also the recipient). In addition, adult stem cells do not have the tumorigenic problem of ES cells upon implantation. Using adult stem cells for research and therapy is also advantageous in the sense that embryos do not have to be destroyed in order to extract the experimental cells.
Current Controversy and Hope for the Future
While the battle over the right to use embryonic stem cells for research is being waged in the public arena, science is moving along with its investigation of adult stem cells to achieve meaningful and beneficial results in the near future. Although highly contested, recent experiments by groups such as Grompe et al. and Catherine Verfaille et al. have suggested that a major setback of using adult stem cells, lack of plasticity, may merely be a myth. If this indeed turns out to be true, stem cells from selected parts of the body could serve therapeutic purposes for a wide range of other tissues. Counter experiments, however, have not been able to validate or repeat such optimistic claims as adult stem cell universal plasticity.
Whether adult stem cell plasticity proves to be fact or fiction remains to be seen. Yet, it is apparent that research in this field is being seriously undertaken using a variety of methods to achieve a greater understanding of these fascinating cells. The exploration of the stem cell and vast potential for its many applications are driving the direction of modern medicine and shaping the 21st century to live up to its designation as the “Century of the Cell” (term employed by Doug Melton, PhD, Harvard stem cell researcher).