Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Biomaterials. 2012 Jul;33(20):5004-12. doi: 10.1016/j.biomaterials.2012.03.065. Epub 2012 Apr 10.
Dynamic cell-microenvironment interactions regulate many biological events and play a critical role in tissue regeneration. Cell homing to targeted tissues requires well balanced interactions between cells and adhesion molecules on blood vessel walls. However, many stem cells lack affinity with adhesion molecules. It is challenging and clinically important to engineer these stem cells to modulate their dynamic interactions with blood vessels. In this study, a new chemical strategy was developed to engineer cell-microenvironment interactions. This method allowed the conjugation of peptides onto stem cell membranes without affecting cell viability, proliferation or multipotency. Mesenchymal stem cells (MSCs) engineered in this manner showed controlled firm adhesion and rolling on E-selectin under physiological shear stresses. For the first time, these biomechanical responses were achieved by tuning the binding kinetics of the peptide-selectin interaction. Rolling of engineered MSCs on E-selectin is mediated by a Ca(2+) independent interaction, a mechanism that differs from the Ca(2+) dependent physiological process. This further illustrates the ability of this approach to manipulate cell-microenvironment interactions, in particular for the application of delivering cells to targeted tissues. It also provides a new platform to engineer cells with multiple functionalities.
动态细胞-微环境相互作用调节许多生物事件，并在组织再生中起着关键作用。细胞归巢到靶向组织需要细胞与血管壁上的粘附分子之间的平衡相互作用。然而，许多干细胞缺乏与粘附分子的亲和力。工程化这些干细胞以调节它们与血管的动态相互作用是具有挑战性和临床重要性的。在这项研究中，开发了一种新的化学策略来工程化细胞-微环境相互作用。这种方法允许将肽缀接到干细胞膜上，而不会影响细胞活力、增殖或多能性。以这种方式工程化的间充质干细胞 (MSC) 在生理剪切应力下表现出对 E-选择素的受控牢固粘附和滚动。首次通过调整肽-选择素相互作用的结合动力学来实现这些生物力学反应。工程 MSC 在 E-选择素上的滚动是由不依赖 Ca(2+)的相互作用介导的，这是一种与 Ca(2+)依赖的生理过程不同的机制。这进一步说明了这种方法操纵细胞-微环境相互作用的能力，特别是在将细胞递送到靶向组织中的应用。它还为工程化具有多种功能的细胞提供了一个新平台。
