The Wisdom in Teeth: Neuronal Differentiation of Dental Pulp Cells

Abstract

Mesenchymal stem/stromal cells (MSCs) are found in almost all postnatal organs. Under appropriate environmental cues, multipotency enables MSCs to serve as progenitors for several lineage-specific, differentiated cell types. In vitro expansion and differentiation of MSCs give the opportunity to obtain hardly available somatic cells, such as neurons. The neurogenic potential of MSCs makes them a promising, autologous source to restore damaged tissue and as such, they have received much attention in the field of regenerative medicine. Several stem cell pool candidates have been studied thus far, but only a few of them showed neurogenic differentiation potential. Due to their embryonic ontology, stem cells residing in the stroma of the dental pulp chamber are an exciting source for in vitro neural cell differentiation. In this study, we review the key properties of dental pulp stem cells (DPSCs), with a particular focus on their neurogenic potential. Moreover, we summarize the various presently available methods used for neural differentiation of human DPSCs also emphasizing the difficulties in reproducibly high production of such cells. We postulate that because DPSCs are stem cells with very close ontology to neurogenic lineages, they may serve as excellent targets for neuronal differentiation in vitro and even for direct reprogramming.

Keywords: dental pulp stem cells; mesenchymal stem cells; neural crest; neural differentiation; reprogramming.

FIG. 1.

Neuronal differentiation of dental pulp cells. (A) During the fourth week of embryonic life—within the ectoderm—dorsally from the neural tube, neural crest cells start to migrate into distinct parts of the developing organs. Later, derivatives of neural crest cells take part in the formation of different craniofacial organs, including the dental pulp complex. (B) Stromal cells from the dental pulp are an easily obtainable source of cells extracted from deciduous or permanent tooth dental. (C) Dental pulp stem cells are spindle-shaped, multipotent stem cells, residing in the stroma of the pulp chamber. After isolation, dental pulp stem cells can start to proliferate in optimal culture conditions. (D) These cells are multipotent and in accordance with their embryonic ontology, under appropriate environmental circumstances, dental pulp stem cells can differentiate into functionally active neuronal cells. (E, F) These in vitro differentiated neuronal cells provide a promising alternative cell source for central nervous system regeneration after ischemic brain damage (E) or spinal cord injury (F).