BioWorld International Correspondent
LONDON - A new type of embryonic stem cell now is available from mice, with characteristics that are "strikingly similar" to those of human embryonic stem cells.
The newly available murine stem cells will accelerate studies into human embryonic stem cells, because they are so alike. That will, scientists predict, speed the development of new therapies for diseases as diverse as diabetes and Alzheimer's disease.
Previously, it only had been possible to isolate embryonic stem cells from a limited number of mouse strains. Following the new development, however, scientists already have isolated the new type of cell from a mouse model of diabetes, and from rats.
This breakthrough raises hopes that researchers will soon be able to isolate embryonic stem cells from a much wider range of mammals, including those of agricultural importance, such as sheep and cattle.
The new type of cells have been called post-implantation epiblast-derived stem cells, or EpiSCs.
Roger Pedersen, professor of regenerative medicine in the department of surgery at the University of Cambridge, UK, told BioWorld International, "We now have an improved model for understanding human diseases that will allow us to bring the awesome power of mouse genetics to bear, using a cell type that seems identical in nature to the human embryonic stem cell."
For example, the mouse model of diabetes develops a very similar disease to that of Type I diabetes in humans, and the genes involved are known to be similar to those identified as linked to Type I diabetes in humans.
Researchers now will be able to knock out each one of these genes in turn, in EpiSCs. It should, in principle, then be possible to add the genetically manipulated EpiSCs to mouse embryos, to make chimeric animals. The resulting animals would contain eggs or sperm that had been derived from the genetically manipulated EpiSCs, and which could give rise to whole animals lacking the gene concerned.
"In this way, we could change a single gene in a diabetic mouse genetic background and find out which genes are causing the disease," Pedersen said. "If similar stem cells could be generated from embryos of domestic livestock, it would enable genetic approaches to produce antibodies or pharmaceuticals on a large scale in the animals' milk. The existing way of doing this is much more difficult."
Two papers published the June 27 advance online publication of Nature report the findings of the two teams that both discovered how to make the new type of stem cell, almost simultaneously.
The first, by Pedersen and his colleagues, is titled: "Derivation of Pluripotent Epiblast Stem Cells from Mammalian Embryos." The second, by Richard Gardner of the University of Oxford, UK, is titled: "New cell lines from mouse epiblast share defining features with human embryonic stem cells."
Pedersen and his group previously had discovered that human embryonic stem cells could be maintained in a culture medium that contained chemicals called activin and nodal, as well as fibroblast growth factor. Work reported in Nature confirmed that those cells could be maintained for very long periods in culture, and yet retain their pluripotency.
Murine embryonic stem cells, however, needed very different techniques for culture. They also maintained their pluripotency in a very different way to human embryonic stem cells.
Pedersen said, "We looked at the numerous differences between human embryonic stem cells and murine stem cells, and we wondered whether these differences represented a species difference, or whether they indicated, for example, a difference in time of development."
Murine embryonic stem cells traditionally have been isolated from mouse embryos at 4.5 days after fertilization, from cells of the inner embryo called the early epiblast. By days six and seven, the cells have formed into a layer called the late epiblast.
Pedersen and his colleagues found that when they isolated the late epiblast cells, they could grow them in culture using the same medium as they used for human embryonic stem cells. Both research teams were able to produce stable cell lines, which were used to work out how the novel cells remain pluripotent, or how they begin to specialize during early development.
Working with researchers at University College London, and the U.S. National Institutes of Health, both groups went on to analyze the molecular characteristics of the newly derived stem cells. That evidence further confirmed the similarity of the novel mouse stem cells to human embryonic stem cells.