a Department of Biology , Faculty of Science, Ferdowsi University of Mashhad , Mashhad , Iran.
b Stem Cells and Regenerative Medicine Research Group , Academic Center for Education, Culture and Research (ACECR), Khorasan Razavi Branch , Mashhad , Iran.
Cell Adh Migr. 2018 Mar 4;12(2):118-126. doi: 10.1080/19336918.2016.1243643. Epub 2018 Feb 27.
Use of mesenchymal stem cells (MSCs) has been introduced as a promising tool, for structural and functional recovery of damaged tissues/organs. Studies have indicated that interactions between chemokine receptors and their ligands have a critical role in homing of MSCs to the site of injury. Although CXCR4 variants have been characterized, the exact role of each transcript in homing has remained unclear. In this study, cells were pretreated with various hypoxia-mimicking compounds (valproic acid, cobalt-chloride, and deferoxamine mesylate). Results indicated that both variants of CXCR4 were overexpressed after 24 hours of treatments and their expression could cooperatively induce and promote the cell migration. Moreover, deferoxamine mesylate was more effective in overexpression of variant A (lo), which resulted in higher level of CXCR4 protein and the highest rate of migration of the cells. In conclusion, our findings may have important potential implications in clinical applications, reinforcing the concept that manipulating the expression of specific CXCR4 variants may increase migration of MSCs.
使用间充质干细胞(MSCs)作为一种有前途的工具,用于受损组织/器官的结构和功能恢复。研究表明,趋化因子受体及其配体之间的相互作用在 MSC 归巢到损伤部位中起着关键作用。尽管已经对 CXCR4 变体进行了表征,但每种转录本在归巢中的确切作用仍不清楚。在这项研究中,细胞先用各种模拟低氧的化合物(丙戊酸、氯化钴和甲磺酸去铁胺)预处理。结果表明,两种 CXCR4 变体在处理 24 小时后均过度表达,它们的表达可以协同诱导和促进细胞迁移。此外,甲磺酸去铁胺在变体 A(lo)的过度表达中更有效,导致 CXCR4 蛋白水平更高,细胞迁移率最高。总之,我们的研究结果可能对临床应用具有重要的潜在意义,进一步证实了这样一种观点,即操纵特定 CXCR4 变体的表达可能会增加 MSC 的迁移。