Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-A secretion
Stem cells from human apical papilla decrease neuro-inflammation and stimulate oligodendrocyte progenitor differentiation via activin-A secretion
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DOI：
10.1007/s00018-018-2764-5
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发表时间：
2018-08-01
影响因子：
8
通讯作者：
des Rieux, Anne
中科院分区：
文献类型：
--
作者：
De Berdt, Pauline;Bottemanne, Pauline;des Rieux, Anne
脊髓损伤后的继发性损伤导致不可逆的病变和阻碍修复过程。促炎细胞因子如TNF-α的局部产生可加剧这些事件。还发生少突胶质细胞死亡，随后进行性脱髓鞘导致显著的组织变性。人牙根尖乳头干细胞（SCAP）可以很容易地从成人未成熟牙齿中获得。这提供了一种微创的方法来重新使用这种组织作为干细胞的来源，与脊髓损伤患者的神经组织活检相比。我们通过研究两种可能的作用模式来评估SCAP发挥神经保护作用的潜力：神经炎症的调节和少突胶质祖细胞（OPC）的分化。将SCAP与LPS激活的小胶质细胞、LPS激活的大鼠脊髓器官型切片（SCOS）以及LPS激活的SCOS和脊髓成人OPC的共培养物共培养。我们首次发现SCAP可以诱导炎症脊髓组织中TNF-α表达和分泌的减少，并且可以通过激活素A分泌刺激OPC分化。这项工作强调了SCAP对脊髓损伤修复的潜在治疗益处。
Secondary damage following spinal cord injury leads to non-reversible lesions and hampering of the reparative process. The local production of pro-inflammatory cytokines such as TNF-alpha can exacerbate these events. Oligodendrocyte death also occurs, followed by progressive demyelination leading to significant tissue degeneration. Dental stem cells from human apical papilla (SCAP) can be easily obtained at the removal of an adult immature tooth. This offers a minimally invasive approach to re-use this tissue as a source of stem cells, as compared to biopsying neural tissue from a patient with a spinal cord injury. We assessed the potential of SCAP to exert neuroprotective effects by investigating two possible modes of action: modulation of neuro-inflammation and oligodendrocyte progenitor cell (OPC) differentiation. SCAP were co-cultured with LPS-activated microglia, LPS-activated rat spinal cord organotypic sections (SCOS), and LPS-activated co-cultures of SCOS and spinal cord adult OPC. We showed for the first time that SCAP can induce a reduction of TNF-alpha expression and secretion in inflamed spinal cord tissues and can stimulate OPC differentiation via activin-A secretion. This work underlines the potential therapeutic benefits of SCAP for spinal cord injury repair.