Skin Cell to Brain Cell without a Stem Cell? Hmmm.

This has implications!  You may have heard about this in a recent news story.

Scientists Transform Skin Cells Direct To Brain Cells, Bypassing Stem Cell Stage

Bypassing the stem cell stage, researchers at the Stanford University School of Medicine in California converted mouse skin cells directly into neural precursor cells, the cells that go on to form the three main types of cell in the brain and nervous system. They write about their findings in the 30 January early online issue of the Proceedings of the National Academy of Sciences.

The findings of this and an earlier study question the idea that pluripotency (the ability to become virtually any other cell in the body, a key characteristic of stem cells) is a necessary stage in the conversion of one cell type to another.

In the earlier study, the same team transformed mouse and human skin cells directly into functional neurons. But this study is a substantial advance on the earlier one for two reasons. First, neural precursor cells can not only differentiate into neurons, they can also become either of the two other main types of cell in the nervous system: astrocytes and oligodendrocytes.  And secondly, neural precursor cells are a more useful and versatile end-product for the lab, where they can be cultivated in large numbers for transplantation or drug screening. Together, the two studies raise the possibility that embryonic stem cell research and induced pluripotency could be replaced by a more direct way of making specific cell types for treatments and research.

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This study provides hope for the treatment of a variety of brain disorders. But what, you may ask, does this have to do with skin, other than as a source of new brain cells?

Well, if you can transform skin cells into brain cells, you can also transform skin cells into skin cells. Let’s say old skin cells into new ones. This study challenges the orthodoxy that states you have to go back to the earliest progenitor cells (let’s say embryonic stem cells) in order to access the critical cellular components responsible for maintenance or restoration of cellular “youth”. We are now starting to understand from these and other experiments that cells can be re-programmed not only to be transformed to another functional type (even bypassing stem cells) but that their phenotypic age can be altered. In other words, they can begin to function again like young cells.

If you are familiar with the concept of Hayflick limit, there is a prominent theory (based on what we know happens in cultured cells) which states that states that every cell has a built in limit on the number of times it can divide to produce daughter cells before becoming “senescent” (still alive, but unable to divide). Even stem cells have this limit, at least in culture (it may be different in vivo). We now are beginning to understand that these characteristics are based on the expression (turning on or off) of certain genes. These genes are closely related to the genes being manipulated to cause cells to transform from one type to another, so a better understanding that domain can benefit our antiaging science efforts as well. If a cell can gain a new life by being phenotypically transformed from old to young, then it is likely that whole tissues can be transformed.

So, we watch these sciences advances closely. Our work with cytokines follows a similar track in that we are just beginning to understand how cells that are busy doing things like acting as healers for tissue damage will modulate their communication chemicals (cytokines, which provide the cell-to-cell information necessary to  do the work of maintaining a tissue). Cytokines can also change gene level expression, altering the protein output of cells (especially other cytokines). This is just another form of phenotypic alteration; not at a level where cells are being transformed in tissue type , but just e.g. awakened to a new stimulus to perform some tasks. Like healing.

So, all things cell biology and skin leads back to our mission. Changing skin, from the cells up.