Hyun Cheol Roh

In June 2007, the media broke an exciting scientific story about how stem cells had been created that could replace “immoral” embryonic stem (ES) cells. A Japanese research group led by Dr. Shinya Yamanaka generated induced pluripotent stem (iPS) cells by introducing four genes into adult mouse skin cells. This result was repeated with human skin cells in November 2007.

This exciting discovery suggested that patient-tailored stem cell therapy was just around the corner and longstanding difficult ethical controversies could be at an end.

Since human ES cell lines were first established by Dr. James Thomson in 1998, this topic has generated great excitement because stem cells appeared to be able to replace damaged tissues of patients. For example, stem cells could be used to replace degenerated neuronal cells in Parkinson’s disease patients. However, because isolating ES cells requires the destruction of embryos, the effort has raised heated ethical controversies. In the U.S., these controversies led to limits on federal funding for ES cell research. In addition, practical difficulties in obtaining a sufficient number of embryos have exacerbated the complexity of ES cell research. As an alternative, adult stem cells have been studied, but their limited potential to differentiate into various types of tissues puts the application of adult stem cells in question.

The great promise of iPS cells seemed to be that they could circumvent the difficulties of ES cell research. Since iPS cells are generated from relatively undifferentiated somatic cells of adult human bodies, there is no need to use embryos, and this resolves the ethical concern over embryo destruction as well as the practical difficulty of obtaining embryos. Furthermore, since iPS cells can be derived from an intended host, iPS cells do not have the problem of rejection reactions when they are transplanted back into the host. These appealing features of iPS cells have led many people to suggest that ES cell research should be stopped and all resources should be dedicated to iPS cell research.

However, the situation is not as simple as it first appears. First, the method used to introduce genes into somatic cells may have side effects, such as causing cancer, because it uses viral vector techniques which introduce their own genetic material. Given that a high risk of developing cancer has been reported in the clinical trials of gene therapy using viral vectors to deliver genes, a great deal of research is required to overcome this problem. Second, although it is reported that iPS cells are not fundamentally different from ES cells, this does not mean that they really are the same. Slight differences may produce substantially different consequences, such as variation in the functional ability of tissues or organs when they are regenerated from stem cells. Furthermore, even the use of iPS cells is not fully free of ethical issues because iPS cells may be used for reproductive cloning by generating sperms and eggs from iPS cells. It is clear that several technical and ethical problems will have to be resolved before iPS cell research can proceed to clinical applications.

Despite the problems of iPS cells, they now are the best option we have for future stem cell therapy, and in my view stem cell research should move in the direction of using iPS cells. However, this does not mean that we should stop research on other types of stem cells. Rather, we need to continue research on ES cells and other adult stem cells that have been studied so far. Just as research on ES cells led to the generation of iPS cells, more knowledge of ES cells may help solve other problems of iPS cells. Furthermore, other types of adult stem cells may offer alternative strategies to avoid the problems of iPS cells.

Without a doubt, the creation of iPS cells is a breakthrough in the field of stem cell research. The development of iPS cells as a practical and ethical option shows great promise for the treatment of various types of diseases and injuries, and it will propel us into a new era of stem cell therapy. However, there are undoubtedly scientific and ethical issues that we have not yet appreciated. Research on iPS cells shows great promise, but it is just the beginning of another round of stem cell research. For the good of all parties, in the next round of research, ES cell and other adult stem cell research should be allowed to proceed in tandem with iPS cell research.