Research Shows That We’ve Been Wrong About Stem Cells

This is a simple schematic of a tooth. (click for credit)

This is a simple schematic of a tooth. (click for credit)

Stem cells are a hot topic in biology. Scientists call them “undifferentiated,” because they have not yet specialized to become a specific kind of cell. This means that a stem cell can develop into several different kinds of cells, depending on what the body needs. For example, everyone has stem cells in their bone marrow. Some of those cells (called hemopoietic stem cells) can develop into various kinds of blood cells, while others (called stromal stem cells) can develop into fat cells, bone cells, or cartilage cells. Physicians have used such stem cells to treat certain heart conditions1, and it is expected that as time goes on, more stem-cell-based treatments will be developed.

Of course, bone marrow isn’t the only place in which stem cells reside. In fact, stromal stem cells can also be found in tooth pulp, the soft tissue that is under the tooth’s dentin (see the illustration above). That’s where the blood vessels and nerves of the tooth are found. While scientists have known for a long time that these stem cells are there, how they get there has always been a mystery.

Nina Kaukua and her colleagues weren’t trying to solve that mystery. They were just studying certain kinds of cells in the teeth of mice. These cells, called “glial cells,” are support cells that help the nerve cells (called neurons) do their job. In their research, they were adding a fluorescent chemical to these cells and watching what happened to them over time. What they found was kind of shocking!

They found that some glial cells would move to the pulp and transform into stem cells! Some of those stem cells would later transform into cells that would produce dentin and enamel for the tooth.2 While this may solve the mystery of where stromal stem cells come from in teeth, that’s not the shocking part. The shocking part is what this result implies about our knowledge of stem cells. As the journal Science puts it:3

Development is thought to be one-way: Stem cells produce cells that mature into specific types, such as neurons and glia in nervous systems. But Kaukua et al. found nervous system cells transforming back into stem cells…

In other words, this research seems to indicate that our basic understanding of stem cells is wrong. It has always been thought that in nature, stem cells produce specialized cells, but the reverse never happens. If this research is confirmed, we now know that the reverse can, indeed, happen in nature. One of the other authors on the study said that he expects their result to be confirmed in many other parts of the body:

The fact that stem cells are available inside the nerves is highly significant, and this is in no way unique for the tooth…Our results indicate that peripheral nerves, which are found basically everywhere, may function as important stem cell reserves. From such reserves, multipotent stem cells can depart from the nerves and contribute to the healing and reformation of tissues in different parts of the body.

It will be very interesting to see whether or not his prediction is confirmed. If nothing else, this research indicates that we have a lot more to learn about stem cells!


1. Sheila A. Fisher, Carolyn Dorée, Susan J. Brunskill, Anthony Mathur, and Enca Martin-Rendon, “Bone Marrow Stem Cell Treatment for Ischemic Heart Disease in Patients with No Option of Revascularization: A Systematic Review and Meta-Analysis,” PLoS ONE, June 19, 2013, DOI:10.1371/journal.pone.0064669
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2. Nina Kaukua, Maryam Khatibi Shahidi, Chrysoula Konstantinidou, Vyacheslav Dyachuk, Marketa Kaucka, Alessandro Furlan, Zhengwen An, Longlong Wang, Isabell Hultman, Lars Ährlund-Richter, Hans Blom, Hjalmar Brismar, Natalia Assaife Lopes, Vassilis Pachnis, Ueli Suter, Hans Clevers, Irma Thesleff, Paul Sharpe, Patrik Ernfors, Kaj Fried, and Igor Adameyko, “Glial origin of mesenchymal stem cells in a tooth model system,” Nature 513:551–554, 2014
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3. “Stem Cell Factories Inside Teeth,” Science 345:635, 2014
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  1. Grant Zimmerman says:

    I think there may have been some other hints of this sort of advance in recent years. A paper out of Japan published in Science in 2010 suggested reversibility in murine spermatogonia; “Functional Hierarchy and Reversibility Within the Murine Spermatogenic Stem Cell Compartment”.

    More recently, Hans Clevers has published results suggesting a heterogenous stem cell pool, with stem cells playing roles determined by their stromal niche environments in the intestinal crypts. He has a very fascinating model system he calls the “confetti mouse” that lends itself to dazzling intravital observation of intestinal homeostasis and regeneration. His group detailed some of their findings in a 2014 Nature paper entitled “Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging”. Certainly its a fascinating field of work right now.

    1. jlwile says:

      Thanks for those references, Grant. I will have to read them. I wonder how I missed the one in Science.