April Flowers for redOrbit.com – Your Universe Online
A research team from the University of California, Davis, has found evidence that a promising type of stem cell being considered for a variety of disease therapies is very similar to the type of cells that cause cancer. The cells, known as induced pluripotent stem cells (iPSCs) show promise as a source of replacement cells and tissues to treat injuries, diseases and chronic conditions. Although the iPSCs have the potential for such good, scientists have to move cautiously because they could also cause malignant cancer, according to the team’s study published online in the journal Stem Cells and Development.
“This is the first study that describes the specific molecular pathways that iPSCs and cancer cells share from a direct comparison” said Paul Knoepfler, associate professor of cell biology and human anatomy. “It means that much more study is required before iPSCs can be used clinically. However, our study adds to a growing knowledge base that not only will help make stem cell therapies safer, but also provide us with new understandings about the cancer-causing process and more effective ways to fight the disease.”
Cell biologists have been able to induce specialized, differentiated cells — such as those obtained from the skin or muscle of adult humans — to become iPSCs since 2007. Like embryonic stem cells, iPSCs are pluripotent, meaning they can become any type of cell and have the potential for being used in treatments for a variety of human diseases. This is a fundamentally new type of clinical care known as regenerative medicine.
The production of iPSCs avoids the controversy that surrounds embryonic stem cells (ES), making them particularly important. They can also be taken from a patient’s own skin and induced to produce other needed tissues, making the chances of immunologic rejection extremely low, eliminating the need to take immunosuppressive drugs.
Earlier studies indicate that both ES and iPSCs pose some health risks. There is an increasing amount of evidence that suggests pluripotency may be related to rapid cellular growth, which is a characteristic of cancer. Both types of stem cells are well known by scientists to have the propensity to cause teratomas, a benign tumor that consists of many different cell types. This new study from UC Davis demonstrates that iPSCs — as well as ES cells — share significant similarities to malignant cancer cells.
The research team compares iPSCs to a form of malignant cancer known as oncogenic foci that are also produced in laboratories. These are used by scientists to create models of cancer, particularly sarcoma. The scientists contrasted the different cells’ transcriptomes, comprised of the RNA molecules or “transcripts.” Transcriptomes reflect only the genes that are actively expressed at a given time and therefore provide a picture of actual cellular activity, unlike DNA analysis, which reflects a cell’s entire genetic code whether or not the genes are active.
By analyzing the transcriptomes, the team found that the iPSCs and malignant sarcoma cancer cells are unexpectedly similar. Genes not expressed in iPSCs are also not expressed in the cancer-generating cells, including many that have properties that guide a cell to normally differentiate in certain directions. Both cell types also exhibited similar metabolic activities. This is another indication that they are related cell types.
“We were surprised how similar iPSCS were to cancer-generating cells,” said Knoepfler. “Our findings indicate that the search for therapeutic applications of iPSCs must proceed with considerable caution if we are to do our best to promote patient safety.”
The team suggests that future experimental therapies using iPSCs for human transplants would most often not involve implanting iPSCs directly into a patient. Instead, iPSCs would be used to create differentiated cells in the laboratory, which could then be transplanted into a patient. This would avoid implanting the undifferentiated iPSCs and reduce the risk of tumor development as a side effect. Even trace amounts of residual iPSCs could cause cancer according to the study.
The UC Davis team also found important differences between the cell types that could provide clues to making iPSCs safer. The research team transformed tumor-generating cell types into iPS-like cells by manipulating their genetic makeup. The reprogrammed cancer causing cells did not behave exactly like iPSCs. They had a reduced ability to produce different cell types, however the findings are still exciting because they suggest that cancer cells can be reprogrammed into more normal cell types, possibly opening the door to new cancer therapies.
“We found that we could reprogram the cancer cells to behave more akin to normal stem cells,” said Knoepfler. “This suggests that such cancer cell reprogramming could become a new way of treating cancer patients, in essence telling their tumors to turn into normal stem cells.”
The team is continuing to study ways to make iPSCs safer, as well as delving further into the differences between the iPSCs and cancer cells. One avenue that is of interest is targeting specific metabolic pathways to enhance iPSCs formation. Modulating other pathways may improve safety.