Banner by Meghan Carlton and Maria Tian

My Skin Can Do What?  

by Maria Tian

“Yama, come quick! Your male mice are pregnant!” These were the words that a lab technician piped to Shinya Yamanaka early one morning. A very perplexed Yama rushed over to the lab to see the mice and indeed, many of them were so swollen that they did look as if they were pregnant.  Unable to believe his eyes, Yama sacrificed a few of the male mice to dissection. However, instead of fetal mice, he found engrossed livers in the mice abdomens. This result deeply fascinated Yama, and after a thorough investigation of the cause, he discovered a protein that was heavily expressed in the large liver tumors: NAT1, or N-acetyltransferase, a protein found to play a role in the breakdown of drugs. Yama discovered that NAT1 was essential to ES (embryonic stem) cells’ pluripotent abilities, which led to the mouse liver`s tumorigenic growth.  Yama quickly became interested in the regenerative properties and biology of ES stem cells. The discovery of the engrossed mouse livers eventually led Yama to pose larger research questions and form two important conclusions: 1) Somatic cells have the potential to transform into ES cells 2) Never take the things that the lab technician says literally.

In 2012, Shinya Yamanaka won the Nobel Prize in Physiology or Medicine for his discovery of IPS (Induced Pluripotent Stem) Cells.  This discovery was a major breakthrough in the field of cell regenerative therapy since the stem cells utilized in therapies at the time had to be derived from embryos.  Presently, this still remains a major ethical controversy among scientists, medical professionals, and the general public as the embryos are destroyed in the ES cell harvesting process. In IPS cells, stem cells can be generated from a patient’s own epithelial cells. These skin cells have the ability to mimic the transformative properties of ES cells to become any other cell in the body. This process not only evades any ethical controversy, but also creates a discrete and personalized treatment plan for patients.

Yama discovered there are four factors that are essential to effective transformation of skin cells to IPS cells: Sox2, Klf4, Oct3/4, and C-myc.  Sox2 is especially important in maintaining stem cell properties and stem cell proliferation, also called “self-renewal.” In further studies, Sox2 was discovered to work alongside Oct3/4 to play an essential role in transforming cancerous cells into ES cells.  Although this study is yet early in its development, it provides a glimpse of hope for many that cancer could be cured in the future. C-myc is the only factor that does not play a crucial part in cellular transformation, but is a strong catalyst to ensure high productivity, much like your morning cup of coffee!

Using Yama’s IPS cells, scientists predict many possible applications including tissue replacement and the potential to cure diseases such as diabetes, cardiovascular disease, Parkinson’s Disease, and Alzheimer’s Disease.  One of the greatest advantages of IPS cells is that by using a patient’s own skin cells, physicians can exceptionally improve treatment and eliminate the risk of tissue rejection. By exposing potential medications to the patient’s reprogrammed cells in a controlled, laboratory setting, physicians can make accurate and informed predictions about how the patient will react to the drugs. This innovation creates peace of mind for patients, knowing that they will not have to suffer through trials of different medications and treatments.  

Thus far, a number of successful transformations have been made from epithelial IPS cells. IPS cells have been used to create retinal cells, mini livers, mini kidneys, and even beating sheets of cardiac tissue!  However, despite immediate experimental success, these phenomena proved ineffective in the long term. Unfortunately, even though rejection by the body is very minimal, the current methods of cell engraftments, or cell transplantations into the human body, are largely ineffective and short-lived. Researchers are working to combat this post-transplant, rapid tissue death in order to improve the diversity and efficiency of IPS cell use.

Fortunately, IPS cell research remains to be a hot topic, as many scientists, including Yama and his team, continue to contribute to the rapid growth in the field and unravel the applications of IPS cells. With this plethora of research, it is possible that we see IPS cell transplantation in human subjects very soon. Yama’s IPS cell discovery revolutionizes cell regenerative therapy and gives hope to many patients facing long waitlists for organ donations, as well as to physicians to treat illnesses in the near future.