BMJ 2002;324:696 ( 23 March )
Susan Mayor London
The ability of adult stem cells to differentiate and proliferate into different cell types has been questioned in research published online last week indicating that they might simply fuse with existing cells, creating genetically mixed cells of questionable medical value.
A group working at the University of Edinburgh tracked the fate of mouse brain cells that were co-cultured with embryonic stem cells. Initial examination indicated that the adult brain cells had reverted to the less specialised status of the undifferentiated stem cells around them. However, the group, whose study appears in the web version of Nature (13 March 2002, www.nature.com), found that the new cells carried transgenic marker and chromosomes derived from the embryonic stem cells.
Genetic analysis confirmed that these new cells actually resulted from the merging of two cell types, so that they had twice the usual number of chromosomes. This suggested that, rather than developing into new cell types, the cells were a genetic mix of the two cell types being cultured together.
Professor Austin Smith, director of the Centre for Genome Research at the University of Edinburgh and one of the authors of the study, commented: "The results indicated that the altered phenotype did not arise by direct conversion of brain to embryonic stem cells, but rather through spontaneous generation of hybrid cells. We propose that transdetermination consequent to cell fusion could underlie many observations otherwise attributed to an intrinsic plasticity of tissue stem cells."
A second study published in the same online issue of Nature, by a group at the University of Florida at Gainesville, showed that bone marrow cells of mice could fuse spontaneously with embryonic stem cells in culture.
Lead researcher Naohiro Terada commented: "Spontaneously fused bone marrow cells can subsequently adopt the phenotype of the recipient cells, which, without detailed genetic analysis, might be interpreted as de-differentiation or transdifferentiation."
The findings raise some doubt about the clinical value of using adult stem cells to produce other cell types, such as brain cells, to be used to repair damaged or diseased tissues. Several studies had shown that adult stem cells could develop into muscle, liver, brain, and heart cells. It was thought that the adult cells reverted to a state similar to that of embryonic stem cells, which are even less specialised, before developing into the new cell types. This was surprising, as it had previously been thought that adult cells were committed to developing into only one class of cell.
The latest studies indicate that researchers should check that the new cell types were not produced by fusion between adult stem cells and other cell types, rather than by differentiation. Professor Smith considers that the new findings underline the need for continuing research into embryonic stem cells, which can differentiate into a variety of different cell types.
He noted: "Our study indicates that calls for a halt to embryonic stem cell research are not scientifically justified and confirms the far-sightedness of the UK legislation."
His group was recently granted one of the first licences to carry out research with embryonic stem cells after approval was given by the House of Lords Select Committee on Stem Cell Research to extend research uses of human embryos to allow research with embryonic stem cells.