Faculty of Science and Technology, Department of Bioscience and Informatics, Keio University, Kanagawa, Japan.
Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi, Japan.
PLoS One. 2021 May 6;16(5):e0251356. doi: 10.1371/journal.pone.0251356. eCollection 2021.
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.
阐明人类疼痛感知的机制需要建立一个包含表达疼痛感应受体的人类细胞的体外疼痛接收模型，这些细胞能够正常发挥神经元的功能。人牙髓间充质干细胞（hDPSCs）是间充质干细胞，是产生人神经元细胞的有前途的候选者，然而，分化的 hDPSCs 的功能特性尚未得到充分表征。在这项研究中，我们通过神经元标记蛋白的表达以及使用 Ca2+ 成像技术检测神经元功能来证明 hDPSCs 的神经元分化。此外，为了确认伤害感受能力，我们将分化的 hDPSCs 的 Ca2+ 反应与大鼠背根神经节 (DRG) 神经元的 Ca2+ 反应进行了比较。这些细胞对谷氨酸、ATP 和瞬时受体电位 (TRP) 通道激动剂表现出相似的反应。由于 TRP 通道与伤害感受有关，分化的 hDPSCs 为体外模型提供了一种有用的人类外周神经元对被解释为疼痛的刺激的反应模型。
