Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London, SW7 2AZ, UK.
Department of Medicine, Imperial College London, London, W12 0NN, UK.
Sci Rep. 2021 Mar 25;11(1):6890. doi: 10.1038/s41598-021-86315-x.
Clinical use of human mesenchymal stem cells (hMSCs) is limited due to their rapid clearance, reducing their therapeutic efficacy. The inflammatory cytokine IL-1β activates hMSCs and is known to enhance their engraftment. Consequently, understanding the molecular mechanism of this inflammation-triggered adhesion is of great clinical interest to improving hMSC retention at sites of tissue damage. Integrins are cell-matrix adhesion receptors, and clustering of integrins at the nanoscale underlies cell adhesion. Here, we found that IL-1β enhances adhesion of hMSCs via increased focal adhesion contacts in an α5β1 integrin-specific manner. Further, through quantitative super-resolution imaging we elucidated that IL-1β specifically increases nanoscale integrin α5β1 availability and clustering at the plasma membrane, whilst conserving cluster area. Taken together, these results demonstrate that hMSC adhesion via IL-1β stimulation is partly regulated through integrin α5β1 spatial organization at the cell surface. These results provide new insight into integrin clustering in inflammation and provide a rational basis for design of therapies directed at improving hMSC engraftment.
由于人骨髓间充质干细胞（hMSCs）的快速清除，其临床应用受到限制，从而降低了它们的治疗效果。炎症细胞因子白细胞介素-1β（IL-1β）激活 hMSCs，并已知可增强其植入。因此，了解这种炎症触发黏附的分子机制对于改善 hMSC 在组织损伤部位的保留具有重要的临床意义。整合素是细胞基质黏附受体，而整合素在纳米尺度下的聚集是细胞黏附的基础。在这里，我们发现 IL-1β 通过以α5β1 整合素特异性的方式增加黏着斑接触，增强 hMSC 的黏附。此外，通过定量超分辨率成像，我们阐明了 IL-1β 特异性地增加了质膜上纳米级整合素α5β1 的可用性和聚类，同时保持了簇面积。总之，这些结果表明，hMSC 通过 IL-1β 刺激的黏附部分受到细胞表面整合素α5β1 空间组织的调节。这些结果为炎症中的整合素聚类提供了新的见解，并为设计旨在改善 hMSC 植入的治疗方法提供了合理的依据。
