Given time, stem cells may mutate

U. MELBOURNE (AUS) / U. SHEFFIELD (UK) — A new study reveals how the genome of 138 stem cell lines of diverse ethnic backgrounds changed when the cells were grown in the laboratory.

Martin Pera, co-author of the paper and chair of stem cell science at the University of Melbourne, says the work “shows clearly that during prolonged culture, stem cells can acquire genetic changes similar to those seen in human cancers.

“While it is reassuring that 75 percent of the stem cell lines studied remained normal after prolonged growth in the laboratory, detecting and eliminating abnormal cells is an absolute prerequisite for clinical use of stem cell products,” he adds.

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Human pluripotent stem cells show promise as a source of cells for regenerative medicine. Human embryonic stem (HES) cells and induced pluripotent stem (iPS) cells are of interest because they can be converted into any cell type in the body and because they are able to grow and divide indefinitely in the laboratory.

However, scientists are concerned that over time the cells can acquire genetic mutations, which may compromise their usefulness for cell therapy.

Researchers led by Peter Andrews from the University of Sheffield analyzed the pattern of genes expressed in 127 HES cell lines and 11 iPS cell lines from ethnically diverse backgrounds. Their findings are reported in the journal Nature Biotechnology.

Although most of the HES cell lines studied retained the normal number of chromosomes, even after prolonged culture, about 20 percent of the cell lines acquired amplifications of a specific region in chromosome 20. Among the small number of iPS cell lines studied, three out of 11 had abnormal karyotypes (chromosome numbers).

The data generated in this study will be useful for understanding the frequency and types of genetic changes affecting cultured hESCs, an important issue in evaluating the cells for potential therapeutic applications.

Pera says the collaborative study from the International Stem Cell Initiative was the largest survey of its kind on the genetic and epigenetic stability of human embryonic stem cell and induced pluripotent stem cells.

Andrew Laslett, co-author on the paper, says, “as well as the scientific outcomes, what has been particularly satisfying about this project is the significant international collaborative networks that have been formed and flourished among the more than 35 laboratories and 125 collaborators.”

Researchers from the National ICT Australia, University of New South Wales, Stem Cells Australia, and Commonwealth Scientific and Industrial Research Organization (CSIRO) contributed to the study that was funded by the International Stem Cell Forum.

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