Dental mesenchymal stem cells

Mesenchymal stem cells have been found in various tissues and act as source for renewal and repair. The mouse incisor tooth continuously grows throughout life, implicating that there are stem cell niches constantly contributing with cells. The composition of these stem cell niches is not fully understood. Here, we show that Schwann cells on the peripheral nerves in the close proximity to the incisor tooth constitute a stem cell niche. Transgenic mouse models were used to label Schwann cells and their progeny in vivo. It was also possible to establish that Schwann cell precursors contributed in tooth development during embryogenesis. In the adult incisor tooth, it was demonstrated that there were a continuous replenishment from Schwann cells with dental mesenchymal stem cells and odontoblasts.

Moreover, through a multi-color reporter line mouse model it was possible to label individual Schwann cells and show their specific contribution and dynamics to tooth organogenesis in adulthood. The dental mesenchymal stem cells were arranged in highly spatialized domain patterns and competed for the opportunity to form odontoblasts. Furthermore, after tooth injury these Schwann cell-derived dental mesenchymal stem cells could be recruited for repair. Thus, these results advocate a novel source of dental mesenchymal stem cells, the peripheral Schwann cells, that throughout life contribute to tooth growth and become involved in regeneration after tooth damage. This might have important implications for the further understanding of adult stem cell populations and their potential use in tissue engineering.

Dental pulps in deciduous and adult human teeth harbor cells with stem/progenitor cell properties and represent an excellent model system to study aging of stromal populations. Aging is tightly connected to self-renewal and proliferation and thus, mapping potential molecular differences in these characteristics between populations constitute an important task. It was hypothesized that genetic profiles of deciduous pulp cells differ from adult pulp cells, due to ontogeny. Deciduous and permanent teeth were collected for tissue sampling, cell culture and isolation. RNA and proteins were extracted with subsequent microarray, quantitative real-time RT-PCR and Western blot analysis while pulp tissue was sectioned for immunohistochemistry stainings.

Results show that there are differentially expressed genes in the deciduous and permanent teeth. Especially genes involved in cell division, mitosis, stemness and ageing are differently expressed in favor of pulp cells from deciduous teeth. Here it is shown for the first time that HMGA2, a neural stem cell marker during embryogenesis, is robustly expressed in deciduous pulp cells. Taken together, the results suggest that cells from deciduous teeth may be more suitable than cells from permanent teeth from a tissue engineering perspective.

List of scientific papers

I. Nina Kaukua, Maryam K Shahidi, Chrysoula Konstantinidou, Vyacheslav Dyachuk, Marketa Kaucká, 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, Igor Adameyko. Glial origin of mesenchymal stem cells in a tooth model system. Nature. (2014) 513:551-554
https://doi.org/10.1038/nature13536

II. Nina Kaukua, Mo Chen, Paolo Guarnieri, Markus Dahl, Mei Ling Lim, Tülay Y. Lindberg, Erik Sundström, Igor Adameyko, Jeremy J. Mao, Kaj Fried. Molecular differences between mesenchymal populations from deciduous and permanent human teeth. Stem Cell Research and Therapy. [Manuscript]