Kim Yong Sook, Park Hye Jung, Hong Moon Hwa, Kang Peter M, Morgan James P, Jeong Myung Ho, Cho Jeong Gwan, Park Jong Chun, Ahn Youngkeun
Cardiovascular Research Institute, Chonnam National University, Gwanju, South Korea.
Front Biosci (Landmark Ed). 2009 Jan 1;14(8):2845-56. doi: 10.2741/3417.
TNF-alpha released from ischemic heart after acute MI increases the production of other cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). Activation of nuclear factor kappa B (NF-kappa B) by TNF-alpha , up-regulates the expression of molecules which are involved in inflammation and cell adhesion. For these reasons, we assessed the extent that treatment of MSC with tumor necrosis factor (TNF)-alpha modifies the characteristics of MSC, important to their engraftment in experimental myocardial infarct. Here, we show that pre-treatment of MSC prior to transplantation with tumor necrosis factor (TNF)-alpha increases adhesiveness, and migration of MSC in vitro and leads to increased expression of bone morphogenetic protein (BMP)-2 by MSC. Moreover, this treatment increases the rate of engraftment of MSC and improves recovery of cardiac function after myocardial infarction. These insights might provide better strategies for the treatment of myocardial infarction.
急性心肌梗死后缺血心脏释放的肿瘤坏死因子-α(TNF-α)会增加其他细胞因子的产生,如白细胞介素-1(IL-1)、白细胞介素-6(IL-6)以及黏附分子,如细胞间黏附分子-1(ICAM-1)。TNF-α激活核因子κB(NF-κB),上调参与炎症和细胞黏附的分子的表达。基于这些原因,我们评估了用肿瘤坏死因子(TNF)-α处理间充质干细胞(MSC)对其特性的影响程度,这些特性对其在实验性心肌梗死中的植入很重要。在此,我们表明在移植前用TNF-α预处理MSC可增加MSC在体外的黏附性和迁移能力,并导致MSC中骨形态发生蛋白(BMP)-2的表达增加。此外,这种处理可提高MSC的植入率,并改善心肌梗死后的心功能恢复。这些见解可能为心肌梗死的治疗提供更好的策略。