Abstract
The adult mammalian central nerve system has fundamental difficulties regarding effective neuroregeneration. The aim of this study is to investigate whether human dental pulp cells (DPCs) can promote neuroregeneration by (i) being differentiated toward neuronal cells and/or (ii) stimulating local neurogenesis in the adult hippocampus. Using immunostaining, we demonstrated that adult human dental pulp contains multipotent DPCs, including STRO-1, CD146 and P75-positive stem cells. DPC-formed spheroids were able to differentiate into neuronal, vascular, osteogenic and cartilaginous lineages under osteogenic induction. However, under neuronal inductive conditions, cells in the DPC-formed spheroids differentiated toward neuronal rather than other lineages. Electrophysiological study showed that these cells consistently exhibit the capacity to produce action potentials, suggesting that they have a functional feature in neuronal cells. We further co-cultivated DPCs with adult mouse hippocampal slices on matrigel in vitro. Immunostaining and presto blue assay showed that DPCs were able to stimulate the growth of neuronal cells (especially neurons) in both the CA1 zone and the edges of the hippocampal slices. Brain-derived neurotrophic factor (BDNF), was expressed in co-cultivated DPCs. In conclusion, our data demonstrated that DPCs are well-suited to differentiate into the neuronal lineage. They are able to stimulate neurogenesis in the adult mouse hippocampus through neurotrophic support in vitro.
Highlights
The adult mammalian central nerve system (CNS) presents inherent difficulties for its effective regeneration following traumatic injuries or neurodegenerative diseases, such as spinal cord injury, stroke and Alzheimer’s disease [1]
This study demonstrated that dental pulp cells (DPCs) have an ability to differentiate toward neuronal lineage and can stimulate neurogenesis in the adult mouse hippocampus by providing neurotrophic support
Immunostaining showed that mesenchymal stem cell markers STRO-1 (Figure 1C) and CD146 (Figure 1D) were both expressed along the blood vessels
Summary
The adult mammalian central nerve system (CNS) presents inherent difficulties for its effective regeneration following traumatic injuries or neurodegenerative diseases, such as spinal cord injury, stroke and Alzheimer’s disease [1]. Stem cell-based therapies were pursued by these two approaches to achieve neuroregeneration: (i) replacing and/or promoting the survival of damaged cells; (ii) providing trophic support to stimulate local neurogenesis [5,6,7]. The transplantation of human embryonic stem (ES) cells, neural stem and progenitor cells (NSPCs), oligodendrocyte precursor cells (OPCs), and bone marrow-derived mesenchymal stem cells (BMSCs) can improve recovery outcomes in animal models of spinal cord injury, and may enhance neurogenesis or replace lost neurons in neurodegenerative diseases [8,9,10,11,12]. There is no direct evidence demonstrating that stem cell-based therapies could improve neurogenesis in neuronal tissues, either in vivo or in vitro
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