Abstract
Dental pulp stem cells (DPSCs) are shown to reside within the tooth and play an important role in dentin regeneration. DPSCs were first isolated and characterized from human teeth and most studies have focused on using this adult stem cell for clinical applications. However, mouse DPSCs have not been well characterized and their origin(s) have not yet been elucidated. Herein we examined if murine DPSCs are neural crest derived and determined their in vitro and in vivo capacity. DPSCs from neonatal murine tooth pulp expressed embryonic stem cell and neural crest related genes, but lacked expression of mesodermal genes. Cells isolated from the Wnt1-Cre/R26R-LacZ model, a reporter of neural crest-derived tissues, indicated that DPSCs were Wnt1-marked and therefore of neural crest origin. Clonal DPSCs showed multi-differentiation in neural crest lineage for odontoblasts, chondrocytes, adipocytes, neurons, and smooth muscles. Following in vivo subcutaneous transplantation with hydroxyapatite/tricalcium phosphate, based on tissue/cell morphology and specific antibody staining, the clones differentiated into odontoblast-like cells and produced dentin-like structure. Conversely, bone marrow stromal cells (BMSCs) gave rise to osteoblast-like cells and generated bone-like structure. Interestingly, the capillary distribution in the DPSC transplants showed close proximity to odontoblasts whereas in the BMSC transplants bone condensations were distant to capillaries resembling dentinogenesis in the former vs. osteogenesis in the latter. Thus we demonstrate the existence of neural crest-derived DPSCs with differentiation capacity into cranial mesenchymal tissues and other neural crest-derived tissues. In turn, DPSCs hold promise as a source for regenerating cranial mesenchyme and other neural crest derived tissues.
Highlights
Dental pulp is a loose connective tissue which contains heterogenous cell populations located in the central part of the tooth [1]
Cells were cultured until passage 14, and grew at a consistent and steady proliferation rate without signs of senescence, suggesting that Dental pulp stem cells (DPSCs) are highly proliferative
In addition to odontoblast-like cell differentiation, we found that some of DPSCs were strongly positive for smooth muscle actin, and those were located adjacent to blood vessels close to HAp/ TC, suggesting pericyte-like phenotype (Figures S10A–S10F, arrowheads)
Summary
Dental pulp is a loose connective tissue which contains heterogenous cell populations located in the central part of the tooth [1]. The multi-differentiation of DPSCs in vitro and in vivo has been variable as described in several reports [3,5,6]. Stem cell populations in adult human dental pulp have been described based on low-affinity nerve growth factor receptor (LNGFR) and b1-integrin expressions, suggesting that the former population is neural crest-derived [10]. In a separate study stem cells isolated from rat embryonic mandibular processes, of neural crest origin, showed multi-differentiation to neural and mesenchymal lineages suggesting DPSCs retain the differentiation capacity of embryonic progenitors [11]. These reports urged us to investigate the origin of DPSCs
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