Investigators have wondered since 2007 whether human induced pluripotent stem cells function the same as embryonic stem cells, which are sourced in primary stage embryos. Although both cell types have the capability to differentiate into any cell in the body, their origins, in embryonic and adult tissue, indicate that they are not equal.
Even though both have huge potential in basic biological investigations in addition to cell and tissue replacement therapy, the newer form, called IPS cells (induced pluripotent stem cells), has two benefits. One advantage is that because they do not require embryos they face less ethical constraints, and the other advantage is that they could be more helpful in cell-replacement therapies – immune rejection would be avoided as they are grown from the patient’s own cells.
However, that cannot be considered identical, until IPS cells have been shown to have equal traits to embryonic stem cells.
In a study published online in Nature Methods, scientists at the University of Wisconsin-Madison reveal the first complete measurement of the proteins created by both types of stem cells.
Joshua Coon, an associate professor of chemistry and biomolecular chemistry who directed the project, explained:
“In a study that looked at four embryonic stem cells and four IPS cells, the proteins turned out to be 99 percent similar.
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.”
Proteins are complicated molecules created by cells for innumerable structural and chemical purposes, and over 6,000 individual proteins were measured by the researchers in the investigation using highly accurate mass spectrometry, a method that measures mass as the first step of identifying proteins.
Doug Phanstiel, who is currently at Stanford University and who worked together with Justin Brumbaugh on the project as graduate students at UW-Madison, said:
“This study is the first comprehensive comparison of proteins
in the two stem cell types.”
Phanstiel, when referring to the investigation of which proteins a cell produces, said:
“From a biological standpoint, what is novel is that this is the first proteomic comparison of embryonic stem cells and IPS cells.”
In essence, each 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 role. Cells regulate the formation and activity of proteins in three ways:
Firstly, by controlling the production of RNA, a molecule that transfers the DNA code to protein-making structures.
Secondly, by controlling the quantity of each protein made.
Thirdly, by adding structures to the protein that regulate when it will be active.
“The new study measured each of these activities. And because we compared four lines of each type of stem cell and the comparisons were run three times, the statistics are extremely robust.”
Coon, who worked with UW-Madison stem-cell pioneer James Thomson on the project, said:
“The new report 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.
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.
The study is not the last word in determining the similarity of the two types of pluripotent stem cells.”
Since clinical uses of either type of stem cells will require that they be transformed into more specialized cells, investigators still need to understand more regarding protein production after a stem cell is differentiated into, for example, a neuron or heart muscle cell.
“This technology 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.”
Written by Grace Rattue