Alpha 7 subunit of nAChR regulates migration of human mesenchymal stem cells.
Alpha 7 subunit of nAChR regulates migration of human mesenchymal stem cells.
复制标题
DOI：
--
复制
发表时间：
2009
影响因子：
--
通讯作者：
I. Schraufstatter;R. Discipio;S. Khaldoyanidi
中科院分区：
文献类型：
--
作者：
I. Schraufstatter;R. Discipio;S. Khaldoyanidi
间充质干细胞（MSCs）向病变组织的有效迁移是实现其再生潜能所必需的。循环细胞进入受损组织的招募是由一个复杂的网络调节的，其中包括非神经胆碱能系统。我们发现人间充质干细胞（hMSCs）表达烟碱乙酰胆碱受体亚基α 7、β 2和β 4。受体激动剂尼古丁引起钙（Ca(++)）流入hMSCs，表明钙离子通道α - 7均聚物介导了这一反应。虽然高浓度的尼古丁（10(5)M）诱导hMSC凋亡，但生理浓度（10(7)M）不会干扰细胞存活。在无毒浓度下，尼古丁增加了hMSCs的自发迁移，而体外hMSCs对C3a和bFGF的趋化性和体内静脉输注hMSCs向骨髓和脾脏的迁移受到抑制。α - 7均聚物的拮抗剂班加罗毒素阻断了尼古丁对趋化因子诱导的hMSCs迁移的抑制作用。这些发现揭示了非神经胆碱能系统参与调节hMSC迁移。
The efficient migration of mesenchymal stem cells (MSCs) to diseased tissues is required for the fulfillment of their regenerative potential. Recruitment of circulating cells into the damaged tissues is regulated by a complex network, which includes the non-neural cholinergic system. We found that human MSCs (hMSCs) express nicotinic acetylcholine receptor subunits alpha 7, beta 2 and beta 4. The receptor agonist nicotine caused calcium (Ca(++)) influx into hMSCs suggesting that the calcium ion channel alpha 7 homopolymer mediated this response. While high concentrations of nicotine (10(5)M) induced hMSC apoptosis, physiological concentrations (10(7)M) did not interfere with cell survival. At non-toxic concentrations, nicotine increased spontaneous migration of hMSCs, whereas chemotaxis of hMSCs toward C3a and bFGF in vitro and migration of intravenously infusion hMSCs into bone marrow and spleen in vivo were inhibited. The antagonist for the alpha 7 homopolymer, bungarotoxin, blocked the inhibitory effect of nicotine on chemotactic factor-induced migration of hMSCs. These findings reveal an involvement of the non-neural cholinergic system in regulation of hMSC migration.