?The Translation of Research Discoveries Into Safe Applicable Procedures Requires High Costs and Long Times?

How have researchers created the different lines of stem cells we have today?

Embryonic stem cells have been derived from blastocysts, i.e. whole embryos at very early stages of development. More recently, lines have been obtained by isolating single cells (blasotomeres) from blastocysts [reviewer's remark: cells have not been taken from blastocysts but from 8-10 cell embryos, well before the blastocyst stage]. This result is particularly interesting because it uses the same procedure that is applied for genetic testing of the embryo (and therefore it does not destroy the embryo).
Adult stem cells are usually isolated from mature tissues and separated from other elements on the basis of their phenotypic traits (expression of stem cell-specific markers) or of their functional features (proliferation and differentiation potential).

There has been a new development in increasing the survival and efficiency of stem cells through rejuvenating specific genes [1]. Can you elaborate?

The approach used by Takahashi and Yamanaka is not to rejuvenate stem cells, but rather to induce stem cell properties in mature cells by modifying their transcriptional network. The result obtained is remarkable since, by inducing only four transcription factors, the authors obtained cells endowed with self-renewal capacities and enlarged differentiative potentialities. In the long run, this approach may prove very important since it may allow the creation of tailored stem cell lines derived from adult cells that can be easily obtained from any patient (e.g. skin or blood cells). However, the way to go is still very long: the cells obtained so far show some interesting features, but also many severe defects. To solve these problems will need more knowledge on the basic biology of embryonic stem cells. In other words, even if such an approach will eventually lead to avoiding the use of human embryos as a source of stem cells, this goal will require a lot more research on human embryonic stem cells.

A recent project cultivated a line of stem cells from arrested embryos [2]. What is your opinion on this?

This goes along the same line as the derivation of stem cell lines from single blastomeres mentioned above. It is another strategy aimed at obtaining embryonic stem cell lines without killing embryos (and, hence, circumventing major ethical concerns). However, the safety of these procedures (in terms of quality and properties of the obtained cells) has still to be elucidated. In general, these results represent proofs of principle: application is still very far (many years at least for neurologic diseases).

Another recent study showed that fully differentiated cells can be more efficient than stem cells for animal cloning and therefore for regenerative medicine [3]. Do we still need stem cells?

I would say that the applications deriving from cloning or stem cells are very different. In any case we still need stem cells at least because we have to unravel and master the molecular mechanisms that make a complex organism from a single multipotent cell. This knowledge is necessary for any therapeutic application that is not merely empirical.

What measures do you believe need to be taken in order to appease the ethical issues of stem cell production?

Ethical as well as political choices have to be taken by common people: it is society that decides what should be done and what should not. In this context the major problem is information. Correct and intelligible information to the public about stem cell research, with balanced emphasis on successes and pitfalls, is a most important issue. Both negative and overoptimistic attitudes will eventually reduce social support for research. Expectations and promises have to be maintained, otherwise people will stop sustaining research. The public has to understand that the actual translation of research discoveries into safe applicable procedures requires high costs and long times. And this is not often explicit when results of stem cell research are communicated by the media.
Another important point refers to commercialization. Stem cells are a complex biotechnological product that will have to be placed on the market sooner or later. Major ethical issues will become apparent about the possibility of selling cells derived from human beings that cannot consent, and also about the property of these cells. The problem is not an immediate one, but it will become critical within a few years.

[1] Takahashi K. and Yamanaka S., Cell, 126, 663 (25 August 2005)
[2] Zhang X., et al., Stem Cells Express, (21 September 2006).
[3] Li-Ying Sung et al, Nature Genetics (1 October 2006)

Ferdinando Rossi is Professor of Neuroscience at the Rita Levi Montalcini Center for Brain Repair, University of Turin.

Interview by Thanh Tam Candice Vu and Gilles Prigent.