New research casts doubt on adult cell research

A pair of papers published this week in Nature have cast doubts on the ability of adult cells to become stem cells, capable of forming any cell in the body.

The two papers both show evidence that putative adult mouse stem cells obtained from adult brain or adult bone marrow and cultured on embryonic stem (ES) cells were a result of fusion of the two cell types, rather than de-differentiation.

Austin Smith of University of Edinburgh and Naohiro Terada of the University of Florida in Gainesville each showed that ES-like cells obtained by culturing differentiated CNS or bone marrow cells with ES cells were actually hybrid cells with double the number of chromosomes.

Smith and his team are principal collaborators with Melbourne company Stem Cell Sciences.

Smith co-cultured foetal mouse brain cells and pluripotent mouse ES cells. After selection for a transgenic marker found only in the brain cells, ES-like cells were isolated that suggested that the brain cells had undergone epigenetic reprogramming. However the cells also carried transgenic markers from the ES cells and were found to contain chromosomes from both cells.

The authors suggested that the two cell types were spontaneously fusing at a low frequency to create pluripotent hybrid cells. They also demonstrated the same phenomenon using adult brain cells.

Caution urged

"This suggests a need for caution with regard to the therapeutic use of adult tissue stem cells. If they only make other tissues by fusing with existing cells rather than producing new cells, their utility for tissue repair and regenerative medicine will be greatly restricted," Smith said.

"While there is justifiably a great deal of interest in the broader applicability of adult stem cells, our findings illustrate that we are currently very ignorant of their biology. It should be noted that although spontaneous cell fusion has been well documented since 1961, this work has been overlooked in the recent reports on tissue stem cells."

"The results strongly question the validity of recent claims that adult stem cells can behave like embryonic stem cells," said Dr Peter Mountford, CEO of Stem Cell Sciences.

Similar results were obtained by Terada using mouse bone marrow cells and ES cells. Again, cells appeared to have been de-differentiated, but contained chromosomes from both cell types. In this case the cells only fused in the presence of IL-3.

Both authors warn that recent studies showing apparent de-differentiation of cells to a pluripotent state or transdifferentiation of cells from one tissue to another may be explained by spontaneous cell fusion. As both of these studies were carried out in vitro, further confirmation will be sought in animal models.

The result has significant implications for the current debate about adult-derived stem cells versus ES cells. Opponents of ES cell research have suggested that stem cells derived from adult tissue would be a suitable alternative.

The Federal government is considering a ban on the use of spare IVF embryos for ES cell research - a move which has angered researchers in Australia who believe that a ban would severely limit the research performed here and force stem cell research overseas.

"The findings clearly highlight the need for continuing research in both ES cells and adult stem cells," Mountford said. "We would be very surprised if valuable contributions to human health were not gained from both approaches.

Smith said that if nothing else, his group's research indicated that calling for a halt to embryonic stem cell research was not scientifically justified and confirmed "the far-sightedness of the UK legislature in approving embryonic stem cell derivation and research."

For more information:

Terada, N et al. Bone marrow cells adopt phenotype of other cells by spontaneous cell fusion. Nature, Advanced online publication DOI: nature730 , (2002).

Ying, Q-L, Nichols, J, Evans, E & Smith, AG. Changing potency by spontaneous fusion. Nature, Advanced online publication DOI: nature729, (2002).