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Some stem cell methods closer to "gold standard" than others

Joseph Ecker

Joseph Ecker, co-director of the Center of Excellence for Stem Cell Genomics

Researchers around the world have turned to stem cells, which have the potential to develop into any cell type in the body, for possible regenerative and disease therapeutics.

Now, for the first time, a team at Salk’s Genomic Analysis Laboratory, along with collaborators from Oregon Health & Science University and the University of California, San Diego, have shown that stem cells created using two different methods are far from identical. The finding could lead to improved avenues for developing stem cell therapies as well as a better understanding of the basic biology of stem cells.

The researchers discovered that stem cells created by moving genetic material from a skin cell into an empty egg cell–rather than coaxing adult cells back into an embryonic state by artificially turning on a small number of genes–more closely resemble human embryonic stem cells, which are considered the gold standard in the field.

“These cells created using eggs’ cytoplasm have fewer reprogramming issues, fewer alterations in gene expression levels and are closer to real embryonic stem cells,” says co-senior author Joseph Ecker, co-director of the Center of Excellence for Stem Cell Genomics. The results of the study were published in Nature.

Human embryonic stem cells are directly pulled from unused embryos discarded from in-vitro fertilization, but ethical and logistical quandaries have restricted their access. Most commonly, scientists create induced pluripotent stem (iPS) cells by starting with adult cells and adding a mixture of genes that, when expressed, regress the cells to a pluripotent stem-cell state. Researchers can then coax the new stem cells to develop into cells of particular tissues, giving scientists a valuable model for studying human disease in the lab.

Over the past year, a team at OHSU built upon a technique called somatic cell nuclear transfer to transplant the DNA-containing nucleus of a skin cell into an empty human egg, which then naturally matures into a group of stem cells.

Ecker, holder of the Salk International Council Chair in Genetics, teamed up with Shoukhrat Mitalipov, developer of the new technique, and UCSD assistant professor Louise Laurent, to compare the approaches. The team created four lines of nuclear transfer stem cells all using eggs from a single donor, along with seven lines of iPS cells and two lines of the gold standard, embryonic stem cells. All cell lines had nearly identical DNA content contained within them.

But when they looked closer at the cells, the researchers spotted some differences: the patterns of methylation–chemical flags that are added to genes to control their expression–varied between the cell lines. And when the investigators looked at patterns of actual gene expression–by measuring the levels of particular RNA strands produced by each cell– the differences continued. Once again, nuclear transfer cells had RNA levels closer to embryonic stem cells, making them more accurate for basic research and therapeutic studies.

If researchers can pin down what it is within an egg that drives the production of pluripotent stem cells, they may be able to integrate that knowledge into iPS cell methods to improve stem cell therapy for disease.