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

Authors

  • Agnes Arthur,

    1. The Australian Research Council, Centre for the Molecular Genetics of Development, University of Adelaide, Adelaide, Australia
    2. School of Molecular and Biomedical Science (Genetics), University of Adelaide, Adelaide, Australia
    3. Mesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science, Hanson Institute/Adelaide University, Adelaide, Australia
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  • Grigori Rychkov,

    1. School of Molecular and Biomedical Science (Physiology), University of Adelaide, Adelaide, Australia
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  • Songtao Shi,

    1. School of Dentistry, University of Southern California, Los Angeles, California, USA
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  • Simon Andrea Koblar,

    1. The Australian Research Council, Centre for the Molecular Genetics of Development, University of Adelaide, Adelaide, Australia
    2. School of Molecular and Biomedical Science (Genetics), University of Adelaide, Adelaide, Australia
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  • Stan Gronthos Ph.D.

    Corresponding author
    1. Mesenchymal Stem Cell Group, Division of Haematology, Institute of Medical and Veterinary Science, Hanson Institute/Adelaide University, Adelaide, Australia
    • Bone and Cancer Laboratories, Division of Hematology, Institute of Medical and Veterinary Science/Hanson Institute, Frome Road, Adelaide 5000, SA, Australia. Telephone: +61-8-8222-3460; Fax: +61-8-8222-3139
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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 neuronal-specific 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 cell-therapeutic paradigms to treat neurological disease.

Disclosure of potential conflicts of interest is found at the end of this article.

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