For the young scientist starting out now in the field of stem cell research, the horizons are unlimited. Whether your skills are in molecular or cellular biology, bioinformatics, electrophysiology, pharmacology, or the clinic, there is room to make a contribution. Christine Mummery, head of the stem cell group at the Netherlands's Hubrecht Laboratory, gives us a detailed view on current situation and future prospects of stem cell research.
Stem cells have the unique capacity not only to give rise to more stem cells, but also to generate differentiated progeny. They are present at all stages of development and probably exist in all multicellular organisms. In adults, they are essential for tissue repair. Although their existence has been known for decades, the recent isolation of particularly unusual stem cells in humans has attracted overwhelming attention from the media, politicians, ethicists, and the general public. Why? Because on the one hand these stem cells have the capacity to form derivatives of all germ layers of the human body, and so offer unmatched potential for application in tissue repair; but on the other, they are derived from very early human embryos.
Although these embryos would be discarded, as they are no longer required for treatment of a fertility problem, they do represent the beginning of human life and deserve special ethical and moral consideration. There is evidence that chronic disabilities such as spinal cord lesions, diabetes, and Parkinson?s disease, where replacement of just one cell type restores tissue function, can be treated with differentiated embryonic stem cells. This justifies the use of human embryos for this research, say proponents. Opponents cite recent evidence suggesting that adult stem cells from somatic tissues may have an unexpected plasticity when placed in a nonhomeostatic environment; bone marrow stem cells may then form neural cells and neural stem cells may form bone instead of the expected hematopoeitic or nerve cells, respectively. They argue that there is a realistic alternative stem cell source for cell therapy.
Most of the experiments showing tissue repair using mouse embryonic or bone marrow stem cells have been carried out in mice. Most experiments with human stem cells have only shown that the cells can acquire the phenotype of various differentiated cell types, but have not shown that the cells are functional at the transplantation site. There is only one way to find out the answer to this dilemma on the equivalence or otherwise of embryonic versus adult stem cells: more research. In Western society the population is growing older, the incidence of chronic disabilities which could be treated by stem cell therapy is steadily rising, and the availability of donor organs is not matching the need. Little surprise, then, that there has been an explosion of interest in stem cell research.
Developmental biologists finally have access to cells representing the early stages of human development so that the genetic control of differentiation can now be studied. Tissue engineers have new sources of cells with which to make 3D constructs of bone, skin, and heart tissue. Clinicians have a potential source of neural cells for treating stroke or Parkinson?s victims, and pancreas cells for treating diabetes patients. And biotech companies are registering patents almost daily covering commercial aspects of stem cell technology development. Commercial interests focus on factors that control stem-cell self-renewal, protocols that result in high-efficiency differentiation to specific cell types, gene profiling to mine for new genes that control growth and differentiation, and methods for efficient generation of transgenic stem cell lines.
This research is all aimed at tissue repair strategies, but it also may provide new in vitro models for human disease. For example, cardiologists would be delighted to have human cardiomyocytes in culture bearing mutations in specific ion channels. These mutations are often inherited and predispose people bearing them to sudden death syndrome at a young age. Mice generated from embryonic stem cells in which ion channel genes have been mutated by homologous recombination often have a perfectly normal heart. Possibly, this is because the physiology of the mouse heart differs completely from that of humans, heart rates for example being in the range of 500 to 700 beats per minute as opposed to 50 to 100 bpm in humans. But if homologous recombination could be worked out in human (embryonic) stem cells, then cardiomyocytes with mutations in ion channels could be derived, as well as a large number of other very useful disease models of other tissues.
All of these areas are among the most exciting and challenging of biomedical research today. Understanding stem cell biology may mean we can control stem cell behaviour and harness their power for tissue repair. The United Kingdom plans to set up a human embryonic stem cell bank. In the event that it becomes possible to generate large numbers of specialized cells for transplantation, such a facility would aim to find reasonable tissue matches for patients so that rejection can be tackled using conventional immunosuppressives. Alternatively, adult stem cells from the patient might be reprogrammed to provide genetically identical replacement tissue. In the far future, perhaps somatic nuclei could be reprogrammed directly. The only way to do this now is by nuclear transfer to an enucleated egg cell ("therapeutic cloning").
The United Kingdom, Israel, and Sweden are among the few countries where stem cell isolation from superfluous in-vitro-fertilized embryos is allowed. However, legislation is pending in a number of others, including the Netherlands. The Lower House of Parliament voted for the legislation in October 2001 and the Upper House will vote on 11 June 2002. In the United States, embryonic stem cell isolation is not permitted using federal funds; however, since August 2001, the Bush government accepted registration of 78 human embryonic stem cell lines on which research could be carried out using government finance. Many other countries have since decided to allow research with these "existing cell lines". With this opening, many excellent developmental and cell biologists, geneticists, and physicians have joined the race toward stem cell based therapies.
For the young research scientist starting out now, the horizons are unlimited. Whether your skills are in molecular or cellular biology, bioinformatics, electrophysiology, pharmacology, or the clinic, there is room for contribution. To read more in detail about research on stem cells done in different labs around the world (the Netherlands, UK, US, and elsewhere) click here.
Finally, a word about women in stem cell research. Developmental biology research has traditionally attracted a disproportionate number of women and many of its great international players were and are female: Hogan, Robertson, Martin, McLaren, Lawson, and Beddington (deceased), to name but a few. Understanding development is of enormous benefit in contributing to stem cell biology, so perhaps here also there is particular room for women. In the Netherlands, far too many excellent female natural science students leave research, sometimes under the impression that it is impossible to combine a research career with family life. As a brand-new professor who is also a mother of three children under 12, I would suggest that it is not. And three female postdocs from my group all have successful research careers with five babies between them!