Adult Human Dental Pulp Stem Cells Differentiate Toward Functionally Active Neurons Under Appropriate Environmental Cues

Abstract

Human adult dental pulp stem cells (DPSCs) reside within the perivascular niche of dental pulp and are thought to originate from migrating cranial neural crest (CNC) cells. During embryonic development, CNC cells differentiate into a wide variety of cell types, including neurons of the peripheral nervous system. Previously, we have demonstrated that DPSCs derived from adult human third molar teeth differentiate into cell types reminiscent of CNC embryonic ontology. We hypothesized that DPSCs exposed to the appropriate environmental cues would differentiate into functionally active neurons. The data demonstrated that ex vivo-expanded human adult DPSCs responded to neuronal inductive conditions both in vitro and in vivo. Human adult DPSCs, but not human foreskin fibroblasts (HFFs), acquired a neuronal morphology, and expressed neuronalspecific markers at both the gene and protein levels. Culture-expanded DPSCs also exhibited the capacity to produce a sodium current consistent with functional neuronal cells when exposed to neuronal inductive media. Furthermore, the response of human DPSCs and HFFs to endogenous neuronal environmental cues was determined in vivo using an avian xenotransplantation assay. DPSCs expressed neuronal markers and acquired a neuronal morphology following transplantation into the mesencephalon of embryonic day-2 chicken embryo, whereas HFFs maintained a thin spindle fibroblastic morphology. We propose that adult human DPSCs provide a readily accessible source of exogenous stem/precursor cells that have the potential for use in celltherapeutic paradigms to treat neurological disease. STEM

A two-step strategy for neuronal differentiation in vitro of human dental follicle cells

“…To achieve more advanced neural differentiation we produced NLCCs in NSCM I and differentiated these cells with a protocol that was recently described for neural differentiation of dental pulp stem cells (Arthur et al, 2008). After cultivation on poly-Lornithine and laminin NLCCs attached, spread and formed single cells with neuron-like morphologies (Fig.…”

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

“…DT-MSCs have high proliferative capacity, are clonogenic in vitro, and demonstrate the ability to differentiate into many cell types such as osteoblasts, chondrocytes, adipocytes, myoblasts, endotheliocytes, and melanocytes, as well as neurons and glia (Gronthos 2000;Arthur et al 2008;Zhang et al 2008. Besides their multilineage differentiation and self-renewal capacity, DT-MSCs exhibit immunomodulatory activities and a greater cell growth ability than BM-MSCs.…”

“…Many studies have reported the in vitro formation of neuronal lineage cells from PDLSCs (Kadar et al 2009;Osathanon et al 2013). Particularly, it has been shown that untreated oral stem cells were able to differentiate into functional neurons upon injection into nervous system (Arthur et al 2008).…”

Osteoblastic/Cementoblastic and Neural Differentiation of Dental Stem Cells and Their Applications to Tissue Engineering and Regenerative Medicine

“…As a control, there was no morphological change and no immunostaining of implanted human foreskin fibroblast at same injection area. 59 Many in vitro differentiation studies and in vivo animal studies for neural differentiation of dental stem cells showed that dental stem cells have been proved to have neural differentiation capacity under proper culture condition and have inducing activity to regenerate neuronal defect by promoting host neuron's migration or self-differentiation into neurons in implanted animal. These studies suggest that there may be potential uses of dental stem cells in the field of neural tissue engineering and that these stem cells may one day be used for nerve regeneration.…”