Japanese researchers rewind the fate of tissues in stem cell breakthrough

Embryonic stem cells. My mom told me not to treat them like playthings and Bush told me not to use them in my research. Scientifically, embryonic stem cells are the holy grail of developmental biology. These cells are pluripotent, meaning they can adopt any cell type present in an adult organism. This unrestricted potential allows scientists to test developmental processes in ways completely impossible with differentiated cells. Moreover, embryonic stem cells have important medical implications, as they can be used in regenerative medicine.

However, as demonstrated by the responses of my mother and former President Bush, these extremely valuable tools have been caught in a heated controversy over the past decade. The use of embryonic stem cells requires the death of an embryo. In the case of human embryonic stem cells, this means the death of a human life. However, thanks to persistent research into the process by which pluripotency can be induced, the necessity of these Promethean tools may be a thing of the past.

In two papers recently published in Nature, a team of researchers from the RIKEN Center for Developmental Biology in Kobe, Japan presented a simple method to induce pluripotency. By exposing differentiated cells to external stressors, such as a decreasing pH, these researchers were able to trigger the expression of pluripotent markers. They have termed the process in which fated cells are dedifferentiated by an external stressor stimulus-triggered acquisition of pluripotency (STAP).

Induced pluripotency was first introduced to the scientific world in 2006. While this research was groundbreaking, the techniques this paper describes are extraordinarily cumbersome. Furthermore, the induced pluripotent stem (iPS) cells of this study can only be created with a one percent conversion rate. This left the field of stem cell research stagnant, searching for a viable alternative to embryonic sources.

The techniques and yields of the STAP cells outlined in the recent Nature papers may reinvigorate the field. Haruko Obokata and Yoshiki Sasai, co-authors of the papers and stem-cell researchers at the RIKEN Center, have demonstrated that bacterial toxins, low pH, and physical squeezing can all prompt cells to dedifferentiate, a process observable through pluripotent markers. The conversion rate for STAP cells is much higher than that of iPS cells: 25 percent of the cells undergoing STAP survive the stress and 30 percent of the survivors express pluripotent characteristics.

The results were so impressive that many scientists doubted the validity of the STAP research. In an attempt to put qualms to rest, Obokata demonstrated that the pluripotent markers actually correlated with true pluripotency. She tagged the STAP cells with a fluorescent marker and injected them into a mouse embryo. If the cells were truly pluripotent, then the fluorescent markers would appear in every tissue type of the resulting adult mouse. For the first few trials, the mice were only faintly fluorescent. However, by creating STAP cells out of the differentiated cells of newborn mice rather than those of adults, Obokata was able to generate fully fluorescent adults.

Lingering doubts forced Obokata to revisit her research techniques. She stressed T cells, a type of white blood cell that is one of the most specialized cells in the body and thus the furthest from a pluripotent state. Not only did she observe stress-induced pluripotency with these T-cells, she caught the dedifferentiation process on video. If doubts still persist, Obokata may need to hold a seminar for her fellow scientists and perform her magic in person.

In addition to alleviating technical difficulties and producing pluripotent cells with a higher conversion rate, STAP may be scientifically superior to iPS because the resulting STAP cells can form placental tissues. Neither iPS cells nor the extremely controversial embryonic stem cells can do this.

This could have important implications for cloning. At the moment, the cloning process is very involved: the scientist needs to extract an unfertilized egg, transfer a donor nucleus into the egg, cultivate the resulting cells to an embryo stage in vitro, and then transfer the embryo into a surrogate organism. If STAP cells can create a placenta, they could be transferred directly into the surrogate without additional steps.

Scientists in the field of regenerative medicine, which attempts to replace or regenerate damaged tissues and organs, are keeping a close eye on STAP cell developments. With more research, it may be possible to grow whole organs from STAP cells.

This would greatly ease the current strain on the donor pool. Furthermore, if the STAP cell originators were taken from the organ recipient, these STAP organs may have a lower rate of rejection. Eventually, it may also be possible to directly inject STAP cells into patients to stimulate the body’s repair mechanism.

At the moment, this option seems quite difficult. Stem cells, regardless of origin, divide nearly uncontrollably. Thus, directly injecting STAP cells into patients may lead to cancerous growths. Despite these obstacles, the marriage between STAP cells and regenerative medicine is likely to be productive.