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

Molecular differences between stromal cell populations from deciduous and permanent human teeth

Introduction: Deciduous and permanent human teeth 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 constitutes an important task. Methods: Using specifically designed microarray panels, Real-Time Quantitative Polymerase Chain Reaction (RT q-PCR), Western blot, immunohistochemistry and siRNA-mediated knock down experiments, we have detected a number of molecules that were differentially expressed in dental pulp from deciduous and permanent teeth extracted from young children and adults, respectively. Results: Among the differentially regulated genes, high-mobility group AT-hook 2 (HMGA2), a stem cell-associated marker, stood out as a remarkable example with a robust expression in deciduous pulp cells. siRNA-mediated knock down of HMGA2 expression in cultured deciduous pulp cells caused a down-regulated expression of the pluripotency marker NANOG. This finding indicates that HMGA2 is a pulpal stem cell regulatory factor. In addition to this, we discovered that several proliferation-related genes, including CDC2A and CDK4, were up-regulated in deciduous pulp cells, while matrix genes COL1A1, fibronectin and several signaling molecules, such as VEGF, FGFr-1 and IGFr-1 were up-regulated in the pulp cells from permanent teeth. Conclusions: Taken together, our data suggest that deciduous pulp cells are more robust in self- renewal and proliferation, whereas adult dental pulp cells are more capable of signaling and matrix synthesis

Glial origin of mesenchymal stem cells in a tooth model system

Mesenchymal stem cells occupy niches in stromal tissues where they provide sources of cells for specialized mesenchymal derivatives during growth and repair. The origins of mesenchymal stem cells have been the subject of considerable discussion, and current consensus holds that perivascular cells form mesenchymal stem cells in most tissues. The continuously growing mouse incisor tooth offers an excellent model to address the origin of mesenchymal stem cells. These stem cells dwell in a niche at the tooth apex where they produce a variety of differentiated derivatives. Cells constituting the tooth are mostly derived from two embryonic sources: neural crest ectomesenchyme and ectodermal epithelium. It has been thought for decades that the dental mesenchymal stem cells giving rise to pulp cells and odontoblasts derive from neural crest cells after their migration in the early head and formation of ectomesenchymal tissue. Here we show that a significant population of mesenchymal stem cells during development, self-renewal and repair of a tooth are derived from peripheral nerve-associated glia. Glial cells generate multipotent mesenchymal stem cells that produce pulp cells and odontoblasts. By combining a clonal colour-coding technique with tracing of peripheral glia, we provide new insights into the dynamics of tooth organogenesis and growth