Tuesday, October 9, 2012

Manufacturing Stem Cells: 2012 Nobel Prize in Medicine


The 2012 Nobel Prize in Medicine was awarded October 8, 2012 to Dr. John B. Gurdon  and Dr. Shinya Yamanaka for their discoveries in the induction of pluripotent stem cells from mature cells.

Cells in a developing embryo are said to be pluripotent, or capable of dividing and becoming any cell in the body. These stem cells develop and grow becoming more and more specialized. The traditional dogma has been that cell differentiation is a one way street. For example, cells can turn down the GI tract path, then the intestine path, then become specialized intestinal wall cells that are capable of absorbing nutrients. Once this cell line takes the GI pathway it cannot switch to the neuron pathway or the shoulder muscle pathway.

Every cell in an organism has every piece of DNA that is necessary to code for every part of that organism. Intestinal cells have the information to build a liver, etc. But while intestinal cells have the information to be any other cell, they lose the ability to differentiate into anything but intestinal cells.

New research, and the work of Drs. Gurdon and Yamanaka have turned that concept on its head.

In the early 1960s Dr. Gurdon's ground breaking work inserted frog intestinal cell nuclei into denucleated frog embryos. These frankenstein cells were capable of growing into fully functioning tadpoles. This meant that DNA information locked inside intestinal cells could be released and successfully used.


Dr. Gurdon's work lead to nucleus transfer research, eventually creating mammals like Dolly the famously cloned sheep.

Next came stem cell research. Researchers thought, "if stem cells in an embryo are used to differentiate into any cell in an organism, why can't they be used to build and rebuild cells in another organism." The thought of applying stem cells to a damaged nerve and inducing nerve regeneration is very exciting. This means we could rebuild livers, cure paralysis, maybe even reverse aging. However the source of embryonic stem cells for humans is highly controversial. Maybe these stem cells could be created much like the nuclear transfer system used by Dr. Gurdon.

Dr. Yamanaka had been studying the enzymes that exist in pluripotent embryonic stem cells. He knew from previous research that a specific cocktail of enzyme activity kept stem cells in the primitive pluripotent state. Dr. Yamanaka induced the function of 24 common stem cell enzyme genes in fully differentiated skin cells. Some of these cells seemed to revert to the pluripotent stem cell state. Eventually four genes were identified as the key factors in inducing this state. Using these genes, in 2007, Dr. Yamanaka and Dr. James Thomson’s labs were able to create human induced pluripotent stem cells.

The technology to create these stem cells is now used in laboratories all around the world. This has allowed massive growth in the research on the therapeutic possibilities of stem cell repair in humans. Induced stem cells are heralding a new age in medicine. Dr. Gurdon and Yamanaka's research is old news. Since 2007, induced stem cell research has advanced greatly. They have been seen to repair retinal damage in mice and promote neuronal growth in muscle and nerve tissue. It is a very exciting age in medicine.

So, congratulations to Dr. Grudon and Dr. Yamanaka. Not to mention the $1.5 million prize!





Frisén J., Lendahl, U., & Perlmann T. (2012) Scientific Background: Mature cells can be reprogrammed to become pluripotent. Nobel Committee for Physiology or MedicineNobelprize.org. 10 Oct 2012 http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/advanced.html

Nobel Foundation (2012, October 8). Nobel Prize in Physiology or Medicine 2012 awarded for discovery that mature cells can be reprogrammed to become pluripotent. ScienceDaily. Retrieved October 9, 2012, from http://www.sciencedaily.com­/releases/2012/10/121008082955.htm

Li, Y., Tsai, Y.T., Hsu, C.W., Erol, D., Yang, J., Wu, W.H., Davis, R.J., Egli, D., and Tsang, S.H. Long-term safety and efficacy of human induced pluripotent stem cell (iPS) grafts in a preclinical model of retinitis pigmentosaMol Med., 2012 DOI:10.2119/molmed.2012.00242


Marisa Karow, Rodrigo Sánchez, Christian Schichor, Giacomo Masserdotti, Felipe Ortega, Christophe Heinrich, Sergio Gascón, Muhammad A. Khan, D. Chichung Lie, Arianna Dellavalle, Giulio Cossu, Roland Goldbrunner, Magdalena Götz, Benedikt Berninger. Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal CellsCell Stem Cell, 2012; 11 (4): 471 DOI: 10.1016/j.stem.2012.07.007


Joe V. Chakkalakal, Kieran M. Jones, M. Albert Basson, Andrew S. Brack. The aged niche disrupts muscle stem cell quiescenceNature, 2012; DOI: 10.1038/nature11438


1 comment:

  1. Normally, I think of stem-cell research as exploring new therapies for disease. However, I found an article acclaiming the use of induced-stem cells in research on disease DEVELOPMENT. The research it cited was performed by Slukvin et. al. They published their work on inducing stem cells from a patient with chronic myeloid leukemia. By using a diseased cell line, they hope to find early developmental cues and events that can be used to detect cancer earlier, find therapies targeting these earlier events, and find clues about preventative measures that may be taken. Apparently, using this cell line not only gives insight into earlier events that occur in the development of the disease, but it is also easier to work with in the lab and more efficient to work with. I thought this sounded pretty exciting! I also wanted everyone else to realize that stem-cell research is not just about having direct therapeutic use, but also about more efficient research techniques.

    I couldn't find the original journal article (supposedly published February 4, 2011 in "Blood"), but here is a link to the article discussing the research findings at Phys.org published the same day as the scientific journal article.

    http://phys.org/news/2011-02-stem-cells-unmask-cancer-earliest.html

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