People react differently to the idea of stem cells - many are scandalized by the thought of using a human embryo for lab work, while equally many encourage the research in hopes of developing treatments for various diseases.
However, scientists have more recently been examining the properties of induced pluripotent stem cells rather than the embryonic stem cells that have caused so much controversy.
Induced pluripotent stem cells (iPSCs) are stem cells derived from adult cells. Once mature cells are reprogrammed back into stem cells, they have the ability to self-renew and differentiate into any kind of cell, which seems analogous to the abilities of embryonic stem cells (ES cells).
However, in a joint study between Andrew Feinberg from the Hopkins School of Medicine and George Daley from Harvard University, it has been shown that although the genes altered in ES cells during normal cell differentiation are the same genes altered in iPSCs, there are fundamental differences between iPSCs and ES cells.
Feinberg, Daley and their colleagues studied the epigenetic nature of the iPSCs, or the external chemical modifications to the genome. Although they should be genetically identical to the mature cells from which they were derived, the iPSCs differ in what DNA is copied when the cell divides, even though the instructions for this difference are not included in the DNA sequence.
In order to "see" these differences, the team used a method called methylation to distinguish which genes were turned off or on after replication. Methylation will silence genes, but still will be copied when a cell divides. Researchers can then identify which genes were silenced and categorize them as differentially methylated regions (DMRs).
"We examined DNA methylation, an epigenetic modification involving a chemical change to cytosine. We found thousands of sites throughout the genome that are reprogrammed epigenetically during the creation of induced pluripotent stem cells," Feinberg said.
Feinberg and Daley's lab used methylation to compare the genetics of mature fibroblasts and the iPSCs derived from those same fibroblasts.
"We have identified the regions that change in their DNA methylation profile during the generation of iPS cells, and surprisingly, the very same regions could distinguish the brain from the liver from the spleen," Akiko Doi, a doctoral candidate in Cellular and Molecular Medicine who works with Feinberg, said.
In essence, the methylated regions show that the same genes are involved in epigenetic reprogramming, tissue differentiation and the development of cancer cells. "It suggests that many of the same gene targets are involved in stem cell reprogramming, differentiation and cancer," Feinberg said. However, although this discovery does link the three phenomena, it could lead to potential problems. "It is both good and bad news clinically, because it tells us something new about cancer, but also tells us to be careful about the genes that might be altered during reprogramming," he said.
Here on the Homewood Campus, the Student Society for Stem Cell Research encourages discussion and promotion of research such as Feinberg's, hoping to educate people about the existence and benefits of induced pluripotent stem cells.
In their most recent Journal Club meetings, which are held two to three times a semester, the topic of interest was tumorigenesis. Jeremy Margarette Vidal, a leader in the group, expressed her excitement about Feinberg's study.
"Scientists have already found a way to reprogram a somatic cell so that it can revert back to its early state, so now it's a matter of analyzing every single factor involved in that because it will allow us to know how abnormalities in cell growth arise," she said.
Vidal believes that Feinberg's discovery of the correlation between methylated sites of the iPSCs and of cancer cells is a step closer in formulating effective cancer treatments.
However, part of Feinberg and Daley's results indicated that there are differences between the induced pluripotent and embryonic stem cells that could cause problems when in therapy. It had been commonly believed that iPSCs and ES cells were similar, if not identical, and so the iPSCs could easily replace ES cells under the umbrella of stem cell treatment.
But differences in the behavior of the two types will need further research. "We identified differences between iPS cells and embryonic stem (ES) cells in terms of their DNA methylation profile," Doi said. "These differences are likely to cause complications if iPS cells are used for stem cell therapies, and further work must be done to create iPS cells that resemble ES cells more closely in their epigenetic profile."
Furthermore, the exact source of these differences is still unclear. "Unfortunately we have had to be limited to the cell lines that were approved by President Bush, so we don't know whether the IPSCs themselves are different, or [if] there is something wrong with the so-called presidential ES cells," Feinberg said.
Feinberg's is one example of promising research regarding the epigenetic nature of the two types of stem cells and their relationship to tissue differentiation and carcinogenesis. Although it is widely known among scientists how to reprogram an adult cell into a stem cell, the actual genetics of the two are only just now being studied. Between the open and educational discussions of our own Student Society for Stem Cell Research and understanding the potential of induced pluripotent stem cells, there is hope that effective treatments for diseases such as cancer can be found.
