Has The Holy Grail Been Found In Stem Cell Medicine?
Last week, the scientific world was intrigued by a study in Nature magazine showing that an acidic environment turned adult mouse cells into "pluripotent" stem cells. The researchers called these new pluripotent cells "stimulus-triggered acquisition of pluripotency cells" (STAP). This could have rather game changing consequences in the stem cell field. Notice I said could! This is no doubt a tremendous scientific feat. However we still do not know what road blocks might arise in using these cells. First of all these cells were grown from mice. To take poetic justice from a familiar phrase "what happens in Vegas stays in Vegas" well sometimes what happens in mice sometimes stays in mice. Clinical translation from one species does not always relate to another species. One need look no further than cancer drugs. Sometimes we find some tremendously successful cancer drugs in an animal trial only to find that it has little or no effect on human tissue. I have some specific questions on these cells that I will mention later in this blog.
The simplicity of producing these cells is when a batch of cells was exposed to a "sub-lethal" acidic environment, with a pH of 5.7, for 30 minutes. I am more convinced than ever than stress will trigger many different reactions in cells. This seems to be a prevailing thread in the stem cell field. Stress will make a cell change its characteristics. The cell can become much more powerful accomplishing repair. In one of my blogs from a few months ago I talked about MUSE cells. MUSE cells are called Multilinage Stress Enduring Cells derived from adipose tissue. These are pluripotent like stem cells derived from adipose tissue. They have an uncanny ability to survive. You will remember that MUSE cells were produced when fat tissue was subjected to harsh environments. It sort of sounds familiar. If we substitute the word STAP cell for a MUSE cell we find strikingly similar aspects of these cells. We start seeing a similar pattern. Some type of stress seems to be a a precipitating event in producing these cells.
To investigate whether the STAP cells could occur in mammals some studies were performed by Vacanti, Obokata and their group. They used mice that were bred to carry a gene that glows green in the presence of Oct-4, a protein that is only found in pluripotent cells. The team took a blood sample from the spleen of these mice when they were one week old, isolated white blood cells called lymphocytes, and exposed them to various strong but fleeting physical and chemical stresses. The team then tried to grow the cells in the lab. Not much happened at first some cells died, and the rest still looked like white blood cells. But on the second day, a number of cells began to glow green, meaning they were producing Oct-4. By day 7, two-thirds of the surviving cells showed this pluripotent marker, together with other genetic markers of pluripotency many of which are also seen in embryonic stem cells. The researchers don't know whether the reprogramming they are seeing is initiated by the low pH or by some other type of stress, such as chemical changes happening further down the line. What we may be doing is turning on genes that were previously turned off. The process of genes being turned off is called gene silencing. As we age many of our genes become silenced. Silenced genes can cause disease. We know that young people have many genes that are turned on and thus they seem as a group to avoid disease. As we age these genes become silenced and disease rears its ugly head.
It might just be that the creation of STAP cells is tapping into a fundamental body-repair process of life. I have suspected for some time now that repair depends upon the severity of the injury. If you injure cells significantly enough, so that they almost die, than certain genes may get switched on or off. This may result in a change in the cell's overall controls, meaning all genes have the potential to be switched on again. This may be the essence of life. We may have stumbled onto the master switch of life. This could happen in all tissue in the body under different circumstances.
There are some reports that these cells are totipotent. A pluripotential stem cell can form almost any kind of tissue. Pluripotent cells, such as embryonic stem cells, can form any cell in an embryo but not a placenta. Totipotent cells, however, can form any cell in an embryo and a placenta. These totipotent stem cells have the ability to creat life. The only cells known to be naturally totipotent are in embryos that have only undergone the first couple of cell divisions immediately after fertilization. This may end up in a Pandora's box. Might humanity go down the slippery slope of cloning a human being. I think this is a place most of humanity does not and should not want to go.
The potential for these cells is great. Some of the questions I have about these cells is for instance what about their telomeres. We have taken an adult cell and reprogramed it but what about its telomeres? Would we have the short telomere length that we would expect it a typical mature cell or would the telomeres lengthen? We know that pluripotent and higher stem cells make telomerase. Telomerase is the enzyme that restores the ends of the DNA strains. Every time a cell reproduces it loses a little snippet of DNA. Once the DNA strand approaches a certain critical level the cell becomes programed to die in a process called apotheosis. Telomerase restores the telomere end. Could we potentially use these STAP cells to not only repair damaged cells but maybe reverse aging. It seems that the more we know the less we know.
Thanks Dr. P
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Has The Holy Grail Been Found In Stem Cell Medicine?