Scripps reports breakthrough in creating live mice from skin cells

Scripps Research Institute scientists are reporting a breakthrough in stem cell research in which they successfully created live mice from mouse skin cells, without using embryonic stem cells or cloning techniques that require eggs. This milestone opens the door to the development of exciting therapies, such as using a patient's own cells to grow replacement organs.

The research is reported in the August 2, 2009, advance, online issue of the journal Nature in a paper titled "Adult mice generated from induced pluripotent stem cells."

In this report, a group of Scripps Research scientists, led by Assistant Professor Kristin Baldwin, Ph.D., describes the creation of mice from what are known as induced pluripotent (iPS) cells-stem cells created by reprogramming normal cells taken non-destructively from living animals. While for several years no research team had been able to generate live adult animals from iPS cell lines, the study is part of a trio of new papers showing the feat is possible. Also reporting similar results are two Chinese groups, who published their findings online in Nature and Cell Stem Cell just days ago. Each group used different methods, with the Scripps Research team's protocols offering more successful results by some measures.

"Reprogramming by iPS cell technology is one of the most exciting areas of research right now," says Baldwin, "because these experiments challenge fundamental paradigms in basic biology and, at the same time, contribute to a technology that offers enormous potential for therapeutic advances."

From Skin Cell to Mouse

Since iPS cells were first generated, several years ago, multiple groups have tried to produce mice from them but no live mice were ever born. For unknown reasons, iPS mouse embryos stopped developing about two-thirds of the way through gestation. This led to concerns that iPS cells might be inferior to embryonic stem cells and hinted that reprogramming with four factors might not be the best method to produce pluripotent cell lines from patients. But the Baldwin team was up to the challenge.

The first part of the team's new study involved gathering cells that were already "differentiated," i.e. developed into a particular cell type, such as skin, nerve, or muscle. In this case, the scientists worked with skin cells from fetal mice, though other cell types may also work. Viruses were then used to insert genes coding for four proteins, called reprogramming factors, into these cells' DNA. These reprogramming factors shifted the cells out of their normal differentiated state to a "pluripotent" state resembling that of embryonic stem cells, which allows the cells to produce a wide variety of cell types. This cellular rewiring caused the cells to change their size and shape so that after only 7 to 10 days they could not be visually distinguished from embryonic stem cells.

"It's actually quite remarkable to see," says Baldwin.

Once skin cells were converted into cells that looked like embryonic stem cells, the researchers needed to find out whether the cells acted like embryonic stem cells. If they didn't, the researchers reasoned, the cells might not be useful therapeutically in generating important cell types such as neurons, heart cells, or liver cells.



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