New technique induces cell differentiation

The Institute for Stem Cell Biology and Regenerative Medicine at Stanford University School of Medicine recently published a study on pluripotency in Proceeding of the National Academy of Sciences. The study engages the possibility of repudiating the popularly conceived notion that pluripotency is necessary to achieve transformation from a general cell type into a specific one. Pluripotency is the process by which stem cells become differentiated into specific cell types.

In the study, the skin of mice was converted into neural precursor cells (NPCs). NPCs are, as the name suggests, precursors of neurons, which means that NPCs can develop into neurons along the way. However, the versatility of NPCs — one of the reasons that NPCs are an attractive option for the transformation of skin cells — includes the growth into astrocytes and oligodendrocytes as well.

The employment of this new method to cultivate specialized cells has multiple advantages over mainstream techniques. One traditional method utilizes stem cells. Stem cells, which are biological cells that can divide and differentiate into various cells with specialized functions, are isolated from blastocysts, which are an aggregation of cells that eventually become embryos in mammals.

The harvesting of stem cells requires the destruction of the embryo and instigates great controversy in the field. Furthermore, it is difficult to genetically match the stem cells to the implantation site in the adult.

However, the achievement of induced pluripotency was able to avoid the contravention of current executive laws against embryo destruction. Induced pluripotent cells (iPS cells) are derived from specialized cells from adults that are driven back along their developmental stages to become stem-cell-like cells, which can, in turn, be cultivated in specific environments to re-specialize into different types.

The inherent disadvantage of iPS cells, however, is the necessary screenings for remaining pluripotent cells that did not differentiate. These cells, if overlooked, can be an origin of cancer.

The next step toward artificial cell specialization is transdifferentiation, which is the process of a non-stem cell transforming into a different type of cell. In early 2010, Marius Wernig and his colleagues successfully converted a mouse skin cell into a developed neuron. They later repeated the experiment with human skin cells and successfully cultivated neurons from skin and liver cells. These neurons are termed induced neurons or iN cells.

This brings us back to the artificial growth of neural precursor cells, or NPCs, which as previously mentioned can continue to develop into three types of cells of the nervous system: neurons, astrocytes and oligodendrocytes.

Wernig's lab, highly motivated by their successes of creating iN cells from other types of cells, planned for another milestone experiment: the development of induced NPCs or iNPCs.

They devised an experiment, in which skin cells of mice were infected with a virus that encoded eleven transcription factors prevalent in NPCs (transcription factors are proteins that facilitate the genetic expression of a protein). Results showed hat about 10 percent of the newly cultivated cells have NPC-like behavior.

The researchers eventually reduced the number of transcription factors down to three in order to optimally produce functional iNPCs: Brn2, Sox2 and FoxG1. All of these transcription factors are associated with the production of missing protein important in electric signaling, which is how our nerves are connected together.

The cultivated iNPCs were injected into newborn mice, which were bred to lack myelinated neurons. Our neurons are wrapped with myelin, which is an insulator to contain the electric signaling between each neuron.

After ten weeks, the neurons in the mice were myelinated, as the injected iNPCs converted to oligodendrocytes, which are cells that wrap myelin around neurons. This suggests that iNPCs are functional in animal models.

The usage of these three transcription factors can generate iNPCs at very high efficiency. Another advantage of this method is that unlike iPS cells, the cultures contain homogenous populations — iNPCs — thus deeming screening procedures unnecessary.

The Wernig lab is currently working on replicating the experiment on human skin cells. Although further research must be done to ensure the safety for human applications of iNPCs, these cells may be very useful for studying human diseases on a petri dish. From the controversial embryonic stem cells,to iNPCs, researchers have been discovering more efficient and less controversial means of developing cells.