Peripheral-neuron-like properties of differentiated human dental pulp stem cells (hDPSCs)

Abstract

Elucidating the mechanisms underlying human pain sensation requires the establishment of an in vitro model of pain reception comprising human cells expressing pain-sensing receptors and function properly as neurons. Human dental pulp stem cells (hDPSCs) are mesenchymal stem cells and a promising candidate for producing human neuronal cells, however, the functional properties of differentiated hDPSCs have not yet been fully characterized. In this study, we demonstrated neuronal differentiation of hDPSCs via both their expression of neuronal marker proteins and their neuronal function examined using Ca2+ imaging. Moreover, to confirm the ability of nociception, Ca2+ responses in differentiated hDPSCs were compared to those of rat dorsal root ganglion (DRG) neurons. Those cells showed similar responses to glutamate, ATP and agonists of transient receptor potential (TRP) channels. Since TRP channels are implicated in nociception, differentiated hDPSCs provide a useful in vitro model of human peripheral neuron response to stimuli interpreted as pain.

Influence of gap junctions upon Ca²⁺ propagation from stimulated keratinocytes to DRG neurons

“…The present question is how we can obtain human free nerve endings. One possible answer is the use of human dental pulp stem cells [ 37 , 38 ]. If an in vitro model for a human free nerve ending model in the skin is established, the development of analgesics will advance considerably.…”

Neuronal Cell Differentiation of Human Dental Pulp Stem Cells on Synthetic Polymeric Surfaces Coated With ECM Proteins

“…Therefore, there should be an optimal ECM protein that is suitable for DPSCs differentiation into neuronal cells. However, there is no research to investigate the effect of several ECM proteins as cell culture biomaterials on the differentiation of human DPSCs into neural cells from our database studies, although there are several studies ( Arthur et al, 2008 ; Ebrahimi et al, 2011 ; Zainal Ariffin et al, 2013 ; Chang et al, 2014 ; Feng et al, 2014 ; Kanafi et al, 2014 ; Al-Zer et al, 2015 ; Mattei et al, 2015 ; Cho et al, 2016 ; Young et al, 2016 ; Zhang et al, 2016 ; Geng et al, 2017 ; Sanen et al, 2017 ; Ullah et al, 2017 ; Zhang et al, 2017 ; Ganapathy et al, 2019 ; Hsiao et al, 2020 ; Rafiee et al, 2020 ; Solis-Castro et al, 2020 ; Arimura et al, 2021 ; Darvishi et al, 2021 ; Zheng et al, 2021 ) that address human DPSCs differentiation into neural cells.…”

Dorsolateral prefrontal cortex sensing analgesia

“…Human epidermal keratinocytes and dermal fibroblasts can be easily obtained as commercially available cells, whereas human neurons are difficult to collect. Oka and Ito have attempted to prepare neurons by differentiating human dental pulp stem cells (hDPSC) [ 66 , 67 ] for this purpose. In particular, Arimura and colleagues compared neurons originating from hDPSCs and rat neurons isolated from the dorsal root ganglion (DRG) [ 67 ].…”

“…Oka and Ito have attempted to prepare neurons by differentiating human dental pulp stem cells (hDPSC) [ 66 , 67 ] for this purpose. In particular, Arimura and colleagues compared neurons originating from hDPSCs and rat neurons isolated from the dorsal root ganglion (DRG) [ 67 ]. These 2 different types of neurons responded to some of the same neurotransmitters.…”