Human PLacental eXpanded (PLX) mesenchymal-like adherent stromal cells confer neuroprotection to nerve growth factor (NGF)-differentiated PC12 cells exposed to ischemia by secretion of IL-6 and VEGF
Human PLacental eXpanded (PLX) mesenchymal-like adherent stromal cells confer neuroprotection to nerve growth factor (NGF)-differentiated PC12 cells exposed to ischemia by secretion of IL-6 and VEGF
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DOI：
10.1016/j.bbamcr.2014.11.009
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发表时间：
2015-02-01
影响因子：
5.1
通讯作者：
Lazarovici, Philip
中科院分区：
文献类型：
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作者：
Lahiani, Adi;Zahavi, Efrat;Lazarovici, Philip
间充质干细胞因其分泌保护性抗炎细胞因子和生长因子的能力而成为中风治疗的有效候选者。我们使用已建立的神经生长因子（NGF）分化的嗜铬细胞瘤PC12细胞暴露于氧和葡萄糖剥夺（OGD）然后再灌注的缺血模型，研究了人胎盘间充质样贴壁基质细胞（PLX）的神经保护作用。在最佳条件下，将 2 x 10(5) PLX 细胞添加到跨孔系统中，可为遭受缺血性损伤的 PC12 细胞提供 30-60% 的神经保护。通过 LDH 释放测量的 PC12 细胞死亡被 PLX 细胞或来自暴露于缺血的 PLX 细胞的条件培养基减少，表明因子成分的主动释放。由于神经保护是细胞因子 IL-6 和血管生成因子 VEGF(165) 的重要功能，因此我们在缺血或含氧量正常的条件下使用细胞的选择性 ELISA 测量了它们的分泌。与常氧条件相比，缺血条件下 PC12 和 PLX 细胞共培养的 IL-6 和 VEGF(165) 分泌量显着更高。向受损伤的 PC12 细胞外源补充各 10 ng/ml IL-6 和 VEGF(165) 可提供神经保护作用，这让人想起 PLX 细胞或其条件培养基的神经保护作用。用 240 ng/ml Semaxanib（抗 VEGF(165)）和/或 400 ng/ml 中和性抗 IL-6 抗体预处理后，生长因子以及共培养条件培养基的影响分别降低了 70% 和 20%。因此，PDC 在缺血性 PC12 细胞中诱导的神经保护作用可能部分由 IL-6 和 VEGF(165) 分泌来解释。这些发现也可以解释用这些细胞治疗后在临床试验中看到的治疗效果。 (C) 2014 Elsevier B.V. 保留所有权利。
Mesenchymal stem cells are potent candidates in stroke therapy due to their ability to secrete protective anti-inflammatory cytokines and growth factors. We investigated the neuroprotective effects of human placental mesenchymal-like adherent stromal cells (PLX) using an established ischemic model of nerve growth factor (NGF)-differentiated pheochromocytoma PC12 cells exposed to oxygen and glucose deprivation (OGD) followed by reperfusion. Under optimal conditions, 2 x 10(5) PLX cells, added in a trans-well system, conferred 30-60% neuroprotection to PC12 cells subjected to ischemic insult. PC12 cell death, measured by LDH release, was reduced by PLX cells or by conditioned medium derived from PLX cells exposed to ischemia, suggesting the active release of factorial components. Since neuroprotection is a prominent function of the cytokine IL-6 and the angiogenic factor VEGF(165), we measured their secretion using selective ELISA of the cells under ischemic or normoxic conditions. IL-6 and VEGF(165) secretion by co-culture of PC12 and PLX cells was significantly higher under ischemic compared to normoxic conditions. Exogenous supplementation of 10 ng/ml each of IL-6 and VEGF(165) to insulted PC12 cells conferred neuroprotection, reminiscent of the neuroprotective effect of PLX cells or their conditioned medium. Growth factors as well as co-culture conditioned medium effects were reduced by 70% and 20% upon pretreatment with 240 ng/ml Semaxanib (anti VEGF(165)) and/or 400 ng/ml neutralizing anti IL-6 antibody, respectively. Therefore, PDC-induced neuroprotection in ischemic PC12 cells may be partially explained by IL-6 and VEGF(165) secretion. These findings may also account for the therapeutic effects seen in clinical trials after treatment with these cells. (C) 2014 Elsevier B.V. All rights reserved.