The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro.
The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro.
复制标题
DOI：
10.1016/j.yexcr.2013.08.025
复制
发表时间：
2013-12
影响因子：
3.7
通讯作者：
M. Skardelly;Anja Glien;Claudia Groba;N. Schlichting;M. Kamprad;J. Meixensberger;J. Milošević
中科院分区：
文献类型：
--
作者：
M. Skardelly;Anja Glien;Claudia Groba;N. Schlichting;M. Kamprad;J. Meixensberger;J. Milošević
在同种异体和异种移植中，充分的免疫抑制在移植物存活中发挥着重要作用，尤其是长期存活。免疫抑制药物对神经干/祖细胞命运的影响尚未得到充分探索。本研究的重点是系统地研究以下四种不同免疫治疗策略对人神经祖细胞体外存活/死亡、增殖、代谢活性、分化和迁移的影响：（1）环孢素A（CsA），一种钙调磷酸酶抑制剂； (2)依维莫司(RAD001)，一种mTOR抑制剂； （3）霉酚酸（MPA，霉酚酸酯），肌苷单磷酸脱氢酶抑制剂和（4）泼尼松龙，类固醇。在最低有效浓度 (MEC) 下，我们发现 hNPC 的增殖能力（BrdU 掺入）显着下降，尤其是 CsA 和 MPA，并且 NAD(P)H 依赖性代谢活性发生改变。在这些条件下，所有四种免疫抑制剂的细胞死亡率、神经发生、胶质细胞生成和细胞迁移基本上不受影响，但凋亡细胞死亡除外，MPA 处理显着增加了凋亡细胞死亡。
In allogenic and xenogenic transplantation, adequate immunosuppression plays a major role in graft survival, especially over the long term. The effect of immunosuppressive drugs on neural stem/progenitor cell fate has not been sufficiently explored. The focus of this study is to systematically investigate the effects of the following four different immunotherapeutic strategies on human neural progenitor cell survival/death, proliferation, metabolic activity, differentiation and migration in vitro: (1) cyclosporine A (CsA), a calcineurin inhibitor; (2) everolimus (RAD001), an mTOR-inhibitor; (3) mycophenolic acid (MPA, mycophenolate), an inhibitor of inosine monophosphate dehydrogenase and (4) prednisolone, a steroid. At the minimum effective concentration (MEC), we found a prominent decrease in hNPCs' proliferative capacity (BrdU incorporation), especially for CsA and MPA, and an alteration of the NAD(P)H-dependent metabolic activity. Cell death rate, neurogenesis, gliogenesis and cell migration remained mostly unaffected under these conditions for all four immunosuppressants, except for apoptotic cell death, which was significantly increased by MPA treatment.