LONDON - Treatment of a huge variety of diseases by harvesting and then manipulating a patient's own cells before returning them to the body has inched closer with the discovery that some body cells can be induced to become multipotential stem cells.

Two researchers based in London have shown that precursor cells that under normal circumstances eventually differentiate into specialized central nervous system (CNS) cells can be turned back into CNS stem cells. The results of their experiments are reported in a paper in Science, dated Sept. 8, 2000, titled "Oligodendrocyte Precursor Cells Reprogrammed to Become Multipotential CNS Stem Cells."2

The finding will be of great interest to those trying to develop different kinds of cell therapy - the replacement of dead or abnormal cells with healthy cells. The advantage of stem cells for cell therapy is that they have the potential to differentiate into many different types of cell. But stem cells are rare in the body and therefore difficult to isolate. Precursor cells, which are able to differentiate into just one or two types of cell, are much more numerous, and easier to harvest. If they could be turned back into stem cells, this would avoid the laborious task of obtaining stem cells from the body.

Toru Kondo, postdoctoral research fellow at the Medical Research Council's Laboratory for Molecular Cell Biology at University College London, and Martin Raff, professor of biology at UCL, carried out their study on oligodendrocyte precursor cells. These cells normally turn into oligodendrocytes, cells in the central nervous system that manufacture myelin.

Kondo told BioWorld International: "My major finding is that oligodendrocyte precursor cells, which until now have been thought to be destined to develop only into oligodendrocytes, can go backwards and become, once again, central nervous system stem-like cells." A recent report has suggested, he added, that central nervous system stem cells can produce almost every kind of cell, given the right conditions.

Raff said: "Kondo's study shows that you can take a cell that has been specified for a particular function and make it go backwards to a more primitive state where it can give rise to a number of different cells that are specialized for other functions. Until now, no one knew that this was possible. The fact that you can take a precursor cell and make it return to a stem cell has potential implications for cell therapy because in principle you can then induce the stem cells to become any type of cell that you want."

Kondo purified oligodendrocyte precursor cells from rat optic nerve and cultured them in fetal calf serum for three days. "For reasons which we don't understand," he said, "this enabled the cells to divide in response to a particular growth factor, called basic fibroblast growth factor. After this, I was able to show that the cells had taken on the properties of central nervous system stem cells."

Kondo carried out several experiments to demonstrate that the results obtained were due to the oligodendrocyte precursor cells reverting to a more primitive state, and were not caused by a small number of stem cells contaminating the original population of cells.

Raff said there had been several recent reports of stem cells from one body system being able to repopulate cells in another body system - for example, blood stem cells being able to repopulate nervous system tissue or muscle tissue. Kondo's next experiments will therefore be designed to find out how primitive the cells he obtained are. He said: "I want to know whether I can do the same thing with these cells - can I convert them into muscle cells, for example? The question is whether it is possible to go from a specified precursor cell all the way back to a cell that can give rise to every kind of cell type in the body."

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