Induced pluripotent stem cells (iPSCs) have many characteristics of embryonic stem cells (ESCs), but they also have some differences. Ever since iPSCs were discovered, there has been a great deal of interest in determining if these cells are similar enough to ESCs for their use in clinical settings.
The similarities are striking: (1) iPSCs and ESCs both cell types have the ability to differentiate into any cell in the body; (2) both can cause teratomas when transplanted into mice with nonfunctional immune systems; (3) both can be grown in culture for long periods of time. However, they have different origins; ESCs come from embryos and iPSCs come from adult tissue. Furthermore many of the genes they express are not completely the same.
A recent study by researchers at the University of Wisconsin at Madison has used assessments of the full range of proteins made by iPSCs and ESCs. Their conclusions are 99% of the proteins made by both types of stem cells (they examined four embryonic stem cell lines and four IPS cell lines) are 99% similar.
According to Joshua Coon, principal investigator of the study and associate professor of chemistry and biomolecular chemistry, “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.”
This study used mass spectroscopy to classify each protein made within the cells and this work, which was published in Nature Methods online. This is the first comprehensive comparison of proteins made in the two stem cell types. Cells make proteins for structural, metabolic, and informational purposes, and protein synthesis is often a direct read-out of gene expression, since many genes encode messenger RNAs that are translated into proteins. Doug Phanstiel at Stanford University, who was a contributor to this project , who is now at Stanford University, said, “From a biological standpoint, what is novel is that this is the first proteomic comparison of embryonic stem cells and IPS cells.”
This study also examined the examined all RNAs made by the cells, the proteins synthesized from them, and the concentrations of these molecules. Also because this study compared four lines of each type of stem cell, and the comparisons were run three times, the statistics in this study are exceedingly robust. According to Coon, embryonic stem cells and IPS cells are quite similar. The protein production of an embryonic stem cell was closer to that of an IPS cell than to a second embryonic stem cell.
This study is not the last word in determining the similarity of the two types of pluripotent stem cells. Clinical uses of either type of stem cells will require that they be transformed into more specialized cells, and researchers still need to know more about protein production after stem cells are differentiated into another cell type.
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.”