INSERM UMR-S 1124, Cellules Souches, Signalisation et Prions, Paris, France.
Université Paris Descartes, Sorbonne Paris Cité, UMR-S 1124, Paris, France.
Stem Cells. 2015 Aug;33(8):2586-95. doi: 10.1002/stem.2037. Epub 2015 May 26.
Characterizing stem cell intrinsic functions is an ongoing challenge for cell therapies. Here, we report that two independent A4 and H8 stem cell lines isolated from mouse molar pulp display the overall functions of bioaminergic cells. Both clones produce neurotrophins and synthesize, catabolize, store, and transport serotonin (5-hydroxytryptamine [5-HT]) and dopamine (DA). They express 5-HT1D,2B,7 and D1,3 autoreceptors, which render pulpal stem cells competent to respond to circulating 5-HT and DA. We show that injury-activated platelets are the source of systemic 5-HT and DA necessary for dental repair since natural dentin reparation is impaired in two rat models with monoamine storage-deficient blood platelets. Moreover, selective inhibition of either D1, D3, 5-HT2B, or 5-HT7 receptor within the pulp of wild-type rat molars after lesion alters the reparative process. Altogether our data argue that 5-HT and DA coreleased by pulp injury-activated platelets are critical for stem cell-mediated dental repair through 5-HT and DA receptor signalings.
鉴定干细胞内在功能是细胞疗法的一个持续挑战。在这里，我们报告说，从小鼠磨牙牙髓中分离出来的两个独立的 A4 和 H8 干细胞系表现出生物胺能细胞的整体功能。这两个克隆都产生神经营养因子，并合成、分解代谢、储存和转运 5-羟色胺（5-HT）和多巴胺（DA）。它们表达 5-HT1D、2B、7 和 D1、3 自身受体，使牙髓干细胞有能力对循环中的 5-HT 和 DA 做出反应。我们表明，激活的血小板是系统内 5-HT 和 DA 的来源，这些物质对于牙齿修复是必需的，因为在两种血小板单胺储存缺陷的大鼠模型中，天然牙本质修复受到损害。此外，在损伤后野生型大鼠磨牙牙髓内选择性抑制 D1、D3、5-HT2B 或 5-HT7 受体，改变了修复过程。总的来说，我们的数据表明，牙髓损伤激活的血小板共同释放的 5-HT 和 DA 通过 5-HT 和 DA 受体信号对干细胞介导的牙齿修复至关重要。
