Neuronal Stem Cells Made from Mature Skin Cells

Stem cell researcher Hans Schöler and his colleagues at the Max Planck Institute for Molecular Biomedicine in Münster, Germany, have successfully isolated neural stem cells from completely differentiated skin cells. Workers and Schöler’s lab procured skin cells from mice and exposed them to a cocktail of special proteins called “growth factors,” and concurrently subjected them to specific culture conditions. This induced the skin cells to differentiate into neuronal somatic stem cells. Schöler noted that their research “shows that reprogramming somatic cells does not require passing through a pluripotent stage.” These new approaches to regenerative medicine can produce stem cells in a shorter time period and are also safer for human clinical use.

Pluripotent stem cells have definitely been the darling of stem cell science since their discovery. When exposed to the right environment, pluripotent stem cells differentiate into every type of cell in the body. However, the pluripotency of these cells, while being their grace is also their curse. According to Schöler, “pluripotent stem cells exhibit such a high degree of plasticity that under the wrong circumstances they may form tumors instead of regenerating a tissue or an organ.” However reprogrammed stem cells can provide a way around these dangers, since they are not pluripotent, but Multipotent (they can only give rise to select subset of cell types rather than any cell type). This can give them an edge in terms of safety and therapeutic potential.

To convert skin cells into stem cells, the Max Planck researchers invented an ingenious protocol that combined several different growth factors (proteins that direct cellular growth) in a culture system that grows the cells and encourages their differentiation into stem cells. One of these growth factors is called Brn4, and Brn4 had never been used in reprogramming experiments before. However, Schöler’s group discovered that Brn4 is one of the most powerful inducers of the stem cell fate in skin cells. The reprogramming of mature skin cells into neuronal stem cells is even more effective if the growth factor-treated skin cells are grown in specific culture conditions. Such culture conditions drive the cells to divide faster and, according to Schöler, the cells gradually “lose their molecular memory that they were once skin cells.” Only after a few cell divisions, the newly produced neuronal somatic stem cells are, for the most part, indistinguishable from neuronal stem cells extracted from neural tissue.

There are other reasons that this work from Schöler’s laboratory might be readily applicable to clinical settings. According the Schöler, “The fact that these cells are multipotent dramatically reduces the risk of neoplasm formation, which means that in the not-too-distant future they could be used to regenerate tissues damaged or destroyed by disease or old age; until we get to that point, substantial research efforts will have to be made.” However, these experiments were done with mouse skin cells. In order to show that this protocol could work for human regenerative medicine, Schöler and his colleagues must demonstrate that human skins cells can also undergo a similar transformation. Additionally, it is crucial to show that these skin cell-derived neuronal stem cells are stable over long periods of time in culture and when implanted into laboratory animals.

Schöler concluded with these remarks: “Our discoveries are a testament to the unparalleled degree of rigor of research conducted here at the Münster Institute. We should realize that this is our chance to be instrumental in helping shape the future of medicine.” At this point, the project is still in its initial, basic science stage although “through systematic, continued development in close collaboration with the pharmaceutical industry, the transition from the basic to the applied sciences could be hugely successful, for this as well as for other, related, future projects. The blueprints for this framework are all prepped and ready to go – all we need now are for the right political measures to be ratified to pave the way towards medical applicability.”

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Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).