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I have obtained my PhD in molecular genetics at the John Innes Centre, Norwich, UK, in 1995. After working as a research fellow at the California Institute of Technology (Pasadena, USA),...
Stem cells: great promise, deep questions
6 Jan, 2006 11:13 am
Stem cells have attracted intense public attention because of their potential use in medicine and because of the ethical questions surrounding the use of embryonic stem cells. These are obviously vastly important matters, but from the biologist?s point of view, they are just two facets of a much wider subject. Stem cells are central to the development of complex organisms ranging from plants to humans. The question of why stem cells behave as they do overlaps with long-standing questions in biology, such as why we age, or why many cells with specialized roles lose the ability to renew themselves. Knowing the underlying questions is important not only to understand the difficulties that lie ahead for medical applications, but also to appreciate the full importance of stem cell research.
The need to balance cell division and cell specialization is common to all complex organisms, from plants to humans. Not surprisingly, stem cells are studied not only in humans and other vertebrates, but also in organisms as different as insects, worms and plants. Because some of the features of stem cells are widespread in different organisms, some of the concepts that help us to understand the behaviour of stem cells in humans have originated from work in very different species, such as fruit flies.
A central question in the study of stem cells in all these organisms is why these cells are able renew themselves indefinitely, while specialized cells lose this ability. It is believed that part of the answer relates to the way genes are shut off, some times permanently, as cells acquire more specialized roles that require only a subset of their genes to remain active. This gradual restriction of the genetic repertoire available to each cell is also seen during embryonic development, and it is believed that stem cells retain some of the properties of the cells present in the early embryo, when the genetic repertoire is still wide open.
The relation between the genetic flexibility of embryonic cells and stem cells is illustrated in humans by the fact that the stem cell cultures with the ability to generate the widest variety of specialized cell types have been derived from early embryos. Stem cells, however, remain active in adult organisms, particularly in tissues that turn over quickly, such as the skin and blood. These “adult” stem cells produce a more limited repertoire of specialized cell types than their embryonic counterparts, but do not carry the associated dilemmas related to using human embryos. The advantages and limitations of “adult” and embryonic stem cell lines have been one of the most hotly debated areas in stem cell research.
The question of how stem cells renew themselves, and for how long, also relates to why we age. Because stem cells are the ultimate source for tissue replacement, our loss of the ability to repair tissues as we age is likely to be caused by damage to the stem cells or by a gradual loss of their ability to self-renew. Conversely, over-proliferation of the stem cells is potentially disruptive to the rest of the organism. The proliferation of stem cells, however, is kept in check because it depends on external signals, which are present only in limited regions within the tissues. It is believed that many forms of cancer originate from stem cells that have escaped this type of control.
Thus stem cells are at the center of several long-term questions in biology. They highlight the unity beneath the diversity of life and are important for understanding cancer and aging. And on top of all that, they carry the promise of revolutionary therapies. Although immensely attractive, the potential practical use of stem cells cannot be disentangled from the long-standing and difficult biological questions. This makes the practical use of stem cells more challenging than is usually appreciated, but at the same time more fascinating.
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