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Critical Similarity Between Two Stem Cell Types
Both cell types have the ability to differentiate into any cell in the body, but their origins from an embryo and from adult tissue suggest that they are not identical.
Both cell types have great potential in cell- and tissue-replacement therapy. However, IPS cells, have two advantages: less ethical constraint, as they do not derive from embryos; and, growing them from the patient's own cells would avoid immune rejection.
But until IPS cells are proven to have the same exact traits as embryonic stem cells, they cannot be considered to be identical.
Now researchers at the University of Wisconsin-Madison report the first full measurement of the proteins made by both types of stem cells.
In a study that looked at four embryonic stem cells and four IPS cells, both cell types produced proteins 99 percent similar, says Joshua Coon, an associate professor of chemistry and biomolecular chemistry who directed the project.
"We looked at RNA, at proteins, and at structures on the proteins that help regulate their activity, and saw substantial similarity between the two stem-cell types," he says.
Proteins are complex molecules made by cells for structural organ repairs and chemical identification of toxins such as allergens. The new study measured more than 6,000 individual proteins produced by each cell type using highly accurate mass spectrometry; measuring mass is the first step of identifying proteins.
The study in Nature Methods, published online, is the first comprehensive comparison of proteins in the two stem cell types, says Doug Phanstiel, who is now at Stanford University, and worked with Justin Brumbaugh on the project as graduate students at UW-Madison.
"From a biological standpoint, what is novel is that this is the first proteomic comparison of embryonic stem cells and IPS cells," says Phanstiel, referring to the study of which proteins a cell produces.
In essence, every cell in the body has the genes to make any protein the body might need, but cells make only the proteins that further their own biological niche. Cells regulate the formation and activity of proteins in three ways: first, by controlling the production of RNA, a molecule that transfers the DNA code to protein-making structures; second, by controlling the quantity of each protein made; and third, by adding structures to the protein that regulate when it will be active.
The new study measured each of these activities, Phanstiel says. "And because we compared four lines of each type of stem cell, and the comparisons were run three times, the statistics are extremely robust," he adds.
The new report, Coon says, suggests that embryonic stem cells and IPS cells are quite similar. According to some measurements, the protein production of an embryonic stem cell was closer to that of an IPS cell than to a second embryonic stem cell.
The ability to measure proteins in such detail emerged from improved ways to measure mass, Coon says.
"New technical developments in both our ability to measure a protein's mass accurate to the third or fourth decimal place and to compare the proteins from up to eight different cell lines at a time -- permitted this important comparison for the first time," says Coon.
The study is not the last word in determining the similarity of the two types of pluripotent stem cells, says Coon, who worked with UW-Madison stem-cell pioneer James Thomson, on the project.
Because clinical uses of either type of stem cells will require that they be transformed into more specialized cells, researchers still need to know more about protein production after a stem cell becomes differentiated into a neuron or heart muscle cell, for example.
This technology, Coon says, "is now well-positioned to study how closely molecules contained in these promising cells change after they are differentiated into the cells that do the work in our bodies a critical next step in regenerative medicine."
Original article: http://www.eurekalert.org/pub_releases/2011-09/uow-src090911.php