stem cell research challenged

June Liu

PureInsight | April 1, 2002

Stem cell research has become one of the hottest fields in the biomedical sciences. Pluripotent stem cells were regarded as new panacea. Many biological and medical journals frequently published papers on the high degree of plasticity of stem cells for multilineage cell differentiation (1,2). This capacity of transdifferentiation of stem cells seems to offer much hope by promising to greatly extend the numbers and range of patients who could benefit from transplants, and to provide cell replacement therapy to treat debilitating diseases such as diabetes, Parkinson's and Huntington's disease. However, the ability of stem cells is being called into question, according to two new reports published on March 14 issue of Nature (3,4). In fact, results from some of the previous articles published in top science journals describing the transdifferentiation ability of stem cells are challenged by these two letters to Nature.

Recent studies have shown that stem cells can differentiate into other types of cells. For example, stem cells from blood can give rise to nerve cells after transplantation. This discovery has intrigued many scientists in the biomedical field. However, studies from these two groups demonstrated that stem cells, instead of differentiating into other cells, rather fused with the cells already in the tissue, giving rise to fusion cells with double amounts of DNA. Thus, as Ms. Helen Pearson wrote in the news comment in Nature, “creating genetically mixed-up tissues with unknown health effects.”

One of the groups is from Center for Genome Research, University of Ediburgh in England (3). They took cells from mouse brain and then co-cultured these cells with pluripotent embryonic stem cells. Undifferentiated stem cells were selected by the presence of transgenic markers which were carried only by brain cells. Surprisingly, they found these cells also carried a chromosome from the embryonic stem cells, indicating that these cells are hybrid cells.

Another group is led by Naohiro Terada in the University of Florida in Gainesville (4). They established a culture of adult pluripotent stem cells by nurturing the cells with embryonic stem cells. The generated cells possess the characteristics of multipotent stem cells. However, they found these cells were multiploid (tetraploid or hexaploid). This unexpected result demonstrated that these cells were fusion cells.

The consequences are obvious if these kinds of stem cell techniques were used for clinical purposes. One stem cell researcher, Dr. Diane Krause from Yale University, said, 'The fusion issue is an important one.' She and others must now investigate whether fusion can explain their results, she says, and these experiments are under way. Researchers think this fusion phenomenon may explain some of the previous results that support the hyped hypothesis about the ability of stem cells.

Fred Gage, a scientist working on nerve stem cells at the Salk Institute in La Jolla, California, said, 'It is quite possible that such fusion events have been previously misinterpreted.' Although the frequency of fusion is particularly low - only once in every 10,000-100,000 cells, the authors of one of the papers pointed out that fused cells could become a dominant population when they had a growth or survival advantage over their parental cells by supplementing deficient genes. This implicated that researchers could probably be misled if they just examined the markers of the donor cells and ignored the markers of the host cells.

Maybe these two new reports help to cool down the zeal for implanting stem cells. This, however, it is not bad news because it would be a disaster if this kind of fusion stem cells were used in the clinic to replace a tissue or an organ. In fact, no matter how advanced systems have developed for curing human diseases, self-adjustment is the best way. Recently, there are some scientific reports to support this ancient principle. Placebos, for example, were shown to have an unexpectedly strong effect in Parkinson's disease (5). Findings from other studies have demonstrated that positive emotions play a critical role on suppressing the neuropathology of Alzheimer's disease and cerebrovascular disease (6), (7). The human heart was recently found to have a self-repair function (8). Human life is not merely a flesh body composed of physical organs. The difference between humans and animals is not only the 5% variation in genome sequence. If human beings rely on the re-construction of each organ or tissue of the human body to get rid of diseases, they will confine themselves within the boundary of being high-level animals.

References

1. Brazelton,T.R.,Rossi,F.M.,Keshet,G.I and Blau,H.M From marrow to brain expression of neuronal phenotypes in adult mice. Science 290, 1775-1779 (2000)
2. Mezey,E,Chandross,K.J.,Harta,G.,Maki,R.A and McKercher,S.R. Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290,1779-1782 (2000)
3. Terada, N. et al. Bone marrow cells adopt phenotype of other cells by spontaneous cell fusion. Nature, Advanced online publication DOI: nature 730, (2002).
4. Ying, Q-L., Nichols, J., Evans, E. & Smith, A.G. Changing potency by spontaneous fusion. Nature, Advanced online publication DOI: nature 729, (2002).
5. de la Fuente-Fernandez, R., T.J. Ruth, V. Sossi, M. Schulzer, D.B. Calne, and A.J. Stoessl. 2001. Expectation and dopamine release: mechanism of the placebo effect in Parkinson's disease. Science 293, no. 5532:1164.
6. Danner, D.D., D.A. Snowdon, and W.V. Friesen. 2001. Positive emotions in early life and longevity: findings from the nun study. J Pers Soc Psychol 80, no. 5:804.
7. Snowdon, D.A., L.H. Greiner, and W.R. Markesbery. 2000. Linguistic ability in early life and the neuropathology of Alzheimer's disease and cerebrovascular disease. Findings from the Nun Study. Ann N Y Acad Sci 903:34.
8. Quaini, F., K. Urbanek, A.P. Beltrami, N. Finato, C.A. Beltrami, B. Nadal-Ginard, J. Kajstura, A. Leri, and P. Anversa. 2002. Chimerism of the transplanted heart. N Engl J Med 346, no. 1:5.