The soft, living part of the tooth—tooth pulp—is known to contain a small reserve of stem cells. These stem cells, scientists agree, can help repair damaged teeth, forming both hard and soft tooth tissue. Scientists, however, have been less certain of these stem cells’ origins.

For decades, the tooth-pulp stem cells, known as dental mesenchymal stem cells, were thought to come from neural crest cells. (In this view, neural crest cells migrate in the early head and form ectomesenchymal tissue.) But now, researchers at Karolinska Institutet assert that a significant population of mesenchymal stem cells during development, self-renewal, and repair of a tooth is derived from peripheral nerve-associated glia.

“We have identified a previously unknown type of stem cells that surprisingly enough belong to the nerves of the tooth; these are nerves that would normally be associated with the tooth’s extreme sensitivity to pain,” said Kaj Fried, Ph.D., at the Department of Neuroscience, one of the head researchers responsible for a study into the origins of mesenchymal stem cells. In this study, the researchers used what they considered an eminently suitable model: the continuously growing mouse incisor tooth.

The results of the study appeared July 27 in Nature, in an article entitled, “Glial origin of mesenchymal stem cells in a tooth model system.” The article indicated that the model served its purpose because mesenchymal stem cells that reside in a niche at the tooth apex produce a variety of differentiated derivatives.

“Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts,” wrote the study’s authors. “By combining a clonal color-coding technique with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth.”

The researchers discovered that young cells, which at first are part of the neural support cells, or the glial cells, leave the nerves at an early stage of the fetal development. The cells change their identity and become both connective tissues in the tooth pulp and odontoblasts—that is, the cells that produce the hard dentin underneath the enamel.

At present, we cannot prompt the growth of new teeth in adults, but the possibility of doing seems nearer now that the Karolinska Institutet researchers have introduced the concept of a glial-to-MSC transition. It suggests that Schwann cells and Schwann cell precursors are dormant neural-crest-like cells that can be recruited from nerves and contribute to peripheral tissues.

“The fact that stem cells are available inside the nerves is highly significant, and this is in no way unique for the tooth,” elaborated Igor Adameyko, Ph.D., at the Department of Physiology and Pharmacology, who co-headed the study. “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.”

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