Mammalian Neural Cells

Since its introduction to the public, stem cell research has been a very touchy subject. Many people are turned away by the thought of sacrificing an unborn child for the sake of the advancement of science, and some are still antsy about the banking of cord blood. This public disapproval has lead many researchers to study the use of adult stem cells, and one group has finally found a viable alternative.

When most people think of stem cell research, they automatically think of genetics. Notably, inserting genes into cells and causing mice to grow ears on their backs and tobacco plants to glow like fireflies. I know I used to imagine ominous-looking men in white labcoats and goggles poking and prodding and writing and scratching their chins… and X-men.

Tobacco Plant with Luciferase Gene

But the reality is that X-men aren’t anywhere near the near future of genetics. Although we do know a lot more than we once knew, we still don’t understand a how to decipher an overwhelming majority of the genetic code. The genetic world is a strange and misunderstood world; since scientists don’t know how to control every aspect of it, small adjustments can result in major phenotype changes. Notable example: Sickle Cell Anemia.

It was for this exact reason that Dr. Sheng Ding, leader of the Scripps Reaserch group that led the study, decided to take a different approach. Ding noted that genes and their protein products are not the only factors in controlling how a cell works. There are numerous other molecules that act as signals and activators, among other things. It was this thought that led him to find three molecules that he could use to de-differentiate adult cells past their pluripotent state, in which cells have a large set of adult cells that they can become, and into their totipotent state, in which cells can become any adult cell for the species.

The group focused on skin cells, thus implementing their knowledge of the “mesenchymal to epithelial cell transition,” in which pleuripotent cells lose their ability to become anything but skin cells. The team focused on throwing a wrench in the process of differentiation. If they could stop the production of the proteins that make cell X a type X cell, then maybe they could figure out a way to turn it into another cell type.

Two proteins, called Transforming Growth Factor Beta and Mitogen-Activated Protein Kinase, were the focal points of the team’s efforts because they play a role in the process that they were attempting to stop. After experimenting with a number of chemical agents, they discovered two of interest: ALK5 inhibitor SB43142 and MEK inhibitor PD0325901. Because these chemicals prevented the function of the two proteins of interest, certain steps in the process of differentiation of epithelial (skin) cells couldn’t progress, leading to the de-differentiation of the cell.

Better yet, the old way required almost a month to reach completion; Ding produced results within two weeks… and did I mention there were 200X the number of cells as compared to traditional methods?

In a later interview with Ding, he explained that his method is better for the sake of research because it decreases the number of variables with which to compete. “[...] conventional conditions can be very variable. [...] The advantage of using chemically defined conditions is you know every single component in your culture. When you observe a phenotype, you know the exact condition that controls the environment.”

This research could lead to new medicines sooner than most would expect. One of the highlights of the study was that each of the tested chemicals were those already known to have passed human testing. Who knows, maybe we’ll life to see soldiers regrow lost limbs or defects corrected. Regardless, this is a serious forward step for the field of regenerative medicine and a hallmark for the study of biology.

Image courtesy of:

Nakamura et al., BMC Cell Biology 2007, 8:52 doi 10.1186/1471-2121-8-52

Keith Wood (of DeLuca lab)

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