Turning Back the Clock
Taking the controversy out of stem cells through iPSCs
The topic of stem cells is one of controversy for many people. But lately, research is discovering ever new sources for these amazing cells. Perhaps the most exciting discovery is induced pluripotent stem cells (iPSC). Scientists can quite literally turn back the clock on adult cells, turning them into the oh so fascinating stem cell.
What good are stem cells you might wonder? Stem cell therapy is already in wide use today. The first of which was bone marrow transplants for leukemia patients. In this procedure, bone marrow is taken from a donor and injected into the sick patient in the hopes that the stem cells will establish themselves and differentiate into the healthy cells the leukemia patient lost during chemotherapy. The downside of this treatment is that in order to receive a transplant from someone else, the other person’s genes must match the recipient’s very closely. Even after a close match is found, the recipient of the transplant, more often than not, has to take drugs to prevent their immune system from rejecting the new bone marrow. These drugs are usually taken for the rest of the patient’s life.
What if the donor could be taken out of the picture entirely? What if the cancer patient was able to receive their own cells to produce new bone marrow? They would no longer face the problem of long waiting periods to find a matching donor and transplant rejection would be almost eliminated. iPSC could one day make this possible.
In 2006, the first iPSCs were made by injecting a virus vector into adult skin cells. They were able to induce an embryonic stem cell-like state from these already differentiated adult cells. From there, all that needed to be done was to give the cells the right signals and they could produce any kind of cell in the body. Their discovery resulted in a Nobel Prize in Physiology or Medicine.
Current research is showing that if you place a cell in a stressful environment, they can transform into a “child-like state”, becoming pluripotent stem cells.
One of the first successful experiments to induce this pluripotent state isolated lymphocyte cells from mice and then exposed the cells to a sub-lethal acidic environment (pH of 5.7 for 30 minutes). After 2 days, the cells started to transform into pluripotent stem cells. After 7 days, 2/3 of the surviving cells were pluripotent.
Not only has this been achieved in vitro, iPSCs have also been induced in living mice. A lentivirus delivery system was used to target astrocyte cells. The virus contained different transcription factors and was injected to the striatum of adult mice. Those astrocytes infected with the virus later became neuroblasts (neuron precursor cells), which are normally found in short supply in the adult brain. With a little further digging, they discovered that only one transcription factor was actually necessary to induce this dramatic change: SOX2.
Sadly, physiological conditions were rarely sufficient to induce these neuroblasts to became neurons. They needed a little help from exogenous BDNF and noggin (proteins that promote neuron growth). In spite of this little let down, the study showed that not only is it possible to create iPSCs, but it is also possible to generate proliferating, non-tumorigenic iPSCs in a living organism.
These new “home grown toolkits” open up a world of possibility for stem cell research, without all the controversy. The future for iPSCs holds many therapeutic possibilities. The elimination of graft-versus-host disease would greatly improve therapies for skin grafts, and cancer, among others. It can also open new therapeutic doors for degenerative diseases, macular degeneration, and many other diseases.
The use of your own cells also eliminates many of the roadblocks in current stem cell therapy research. No longer would embryos be necessary, we could use an adult’s own cells for their treatment. Or even possibly develop cell lines to reduce the wait time even more. Further into the future, iPSCs may even be used to print whole organs using 3D printers. The possibilities are out there, just waiting to be discovered.
Bone Marrow Transplant. Medline Plus. http://www.nlm.nih.gov/medlineplus/ency/article/003009.htm
Science Magazine published yesterday (March 10, 2014) that the paper by Haruko Obokata is currently under investigation. No other lab has yet been able to replicate the results using the methods presented in the paper. The images used are also under investigation as some claim they are similar to those published in other papers. For the whole story visit: http://news.sciencemag.org/biology/2014/03/retraction-request-made-more-questions-swirl-around-simple-stem-cell-method
