Department of Orthopedic Surgery, Charles University in Prague, Faculty of Medicine and University Hospital in Hradec Kralove, Hradec Kralove, Czech Republic.
Int Orthop. 2010 Feb;34(1):137-42. doi: 10.1007/s00264-008-0717-6. Epub 2009 Feb 11.
Methotrexate (MTX) released from bone cement showed a useful local effect in animal models of bone tumours. However, local toxic reactions such as impaired wound healing were observed in areas surrounding the MTX-loaded implant. Therefore, we hypothesised that MTX released from bone cement would have harmful effects on human mesenchymal stem cells (MSC)-one of the basic components of bone marrow and tissue reparatory processes. Moreover, elution of MTX was calculated from implants prepared either with liquid or powdered MTX. During the 28-day incubation, the cement compounded with liquid MTX showed the highest elution rate of the drug. MTX released from pellets produced a significant decrease in proliferation of MSC as a consequence of a blockade of their cell cycle in the S/G2 phase. These findings indicate impairment of stem cell function in marginal areas surrounding the MTX-loaded cement and may help to explain problems with regeneration of tissues in these locations.
甲氨蝶呤（MTX）从骨水泥中释放出来，在骨肿瘤的动物模型中显示出了有用的局部效果。然而，在负载 MTX 的植入物周围的区域观察到了局部毒性反应，如伤口愈合受损。因此，我们假设 MTX 从骨水泥中释放出来会对人类间充质干细胞（MSC）产生有害影响——MSC 是骨髓和组织修复过程的基本组成部分之一。此外，还从使用液体或粉末 MTX 制备的植入物中计算了 MTX 的洗脱量。在 28 天的孵育过程中，与液体 MTX 复合的水泥表现出最高的药物洗脱率。MTX 从微球中释放出来，通过阻止 MSC 的细胞周期进入 S/G2 期，导致 MSC 的增殖显著减少。这些发现表明，负载 MTX 的水泥周围的边缘区域的干细胞功能受损，这可能有助于解释这些部位组织再生的问题。
