In recent years the stem cell research community generated a great excitement over the possibility of developing stem cells from a patient’s own skin for the treatment of various conditions like cancer, Parkinson’s and Alzheimer’s disease.
Therapies like this would relinquish the need for using stem cells derived from human embryos and theoretically bypass immunological problems occurring in using cells from one person to treat another, hence avoiding controversy.
However, the development of deriving stem cells from adult cells, called induced pluripotent stem cells (iPSCs), since the article almost five years ago, has raised unique characteristic problems in their use and even their immunological safety has been questioned.
Paul S. Knoepfler, UC Davis associate professor of cell biology and human anatomy believes that finding obstacles in such a new and novel approach is normal and should not stop researchers from actively pursuing their research.
Knoepfler and Bonnie Barrilleaux, a postdoctoral fellow working in Knoepfler’s laboratory, has written a roadmap to detect solutions to the problems identified with iPSCs, which is available online and has been published in the Aug. 5 issue of Journal Cell Stem Cell. Their article “Inducing iPSCs to escape the dish” recommends for research strategies to advance the field more rapidly towards applications for human diseases.
Knoepfler, who also is a faculty member of the UC Davis Genome Center and UC Davis Cancer Center said:
“IPSCs offer the potential to treat many diseases as an alternative or adjuvant therapy to drugs or surgery. Problems that have been identified with their use likely can be overcome, allowing iPSCs to jump from the laboratory dish to patients who could benefit from them.”
The first iPSCs were derived from mouse cells in 2006 and a year later from human cells. Although these cells contain many cells that have the same regenerative properties as human embryonic stem cells, they are derived in a lab from adult cells, such as skin cells, by inducing or forcing them to express specific genes that are normally dormant in that type of cell.
For example, in theory a person’s skin cells could be used to create neurons producing the neurotransmitter dopamine and be delivered to the parts of the brain where dopamine is missing in patients with Parkinson’s disease. Cells could also be created to regenerate heart muscle and blood vessels after heart attacks or neurons following spinal chord injuries. Several laboratories at UC Davis, including the Knoepfler lab, produce and study human iPSCs.
A big advantage favoring the use of iPSCs over stem cells produced from embryos is the elimination of rejection due to immunological differences between donor (embryo) and patient, because the iPSCs would be produced from each individual patient.
However, a recent study on mice with iPSCs showed that tissue rejection might occur in some cases. Knoepfler suggests that this particular study was carried out in the context of tumors, which tend to be highly immunogenic and not applicable for human use.
Although the possibility of human iPSCs avoiding immune attention requires further investigation, Knoepfler insists that iPSCs continues to represent an attractive potential avenue for stem cell-based medicine, in addition to embryonic stem cells.
One fear of using iPSCs or embryonic stem cells is that cells with the ability to turn into many different cell types may grow rampant and produce cancerous tumors, however, Knoepfler highlights that studies involving the implant of large numbers of undifferentiated stem cells into mice were treated with immunosuppressant drugs to reject transplants and therefore made conditions ideal for cancers to arise. He argues that it is unlikely to apply when humans are treated for actual diseases as in such cases the stem cells would be cultivated to have a specific function and the body’s natural immune defenses would be present.
Stem cell therapy has already been successfully used for years to treat leukemia and related bone and blood cancers, representing only the beginning of stem cells to allow their use of repairing almost any tissue that can be used for human therapies because of their “pluripotent’ nature. Using iPSCs could vastly increase the range of diseases open to stem cell treatments, eliminating any safety and ethical concerns of using embryonic stem cells.
Knoepfler stated:
“Dr. Barrilleaux and I argue for a shift in research priorities. Future studies of iPSCs should increasingly focus on issues most relevant to the eventual clinical use of the cells, offering the fastest pathway to treating patients with this potentially powerful therapeutic tool.”
Knoepfler’s personal research comprises analyzing how to control stem cell behavior during normal embryonic development, as well as during healing and regeneration. In addition, he studies how control systems go haywire in developmental disorders and cancer. Knoepfler’s lab uses leading genomics technology to obtain a better understanding of stem cell behavior and how to change this behavior for clinical use.
Written by Petra Rattue