Stem cell membrane engineering for cell rolling using peptide conjugation and tuning of cell-selectin interaction kinetics.

Stem cell membrane engineering for cell rolling using peptide conjugation and tuning of cell-selectin interaction kinetics.
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DOI:
10.1016/j.biomaterials.2012.03.065
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发表时间:
2012-07
期刊:
影响因子:
14
通讯作者:
Anderson, Daniel G.
Anderson, Daniel G.
中科院分区:
工程技术1区
文献类型:
--
作者:
Cheng, Hao;Byrska-Bishop, Marta;Zhang, Cathy T.;Kastrup, Christian J.;Hwang, Nathaniel S.;Tai, Albert K.;Lee, Won Woo;Xu, Xiaoyang;Nahrendorf, Matthias;Langer, Robert;Anderson, Daniel G.

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动态的细胞与微环境相互作用调节许多生物事件,并在组织再生中发挥关键作用。细胞归巢到靶组织需要细胞和血管壁上的粘附分子之间的良好平衡的相互作用。然而,许多干细胞缺乏与粘附分子的亲和力。这是具有挑战性的和临床上重要的工程改造这些干细胞,以调节其与血管的动态相互作用。在这项研究中,开发了一种新的化学策略来设计细胞-微环境相互作用。该方法允许肽缀合到干细胞膜上而不影响细胞活力、增殖或多能性。以这种方式工程化的间充质干细胞(MSC)在生理剪切应力下显示出受控的牢固粘附和在E-选择素上滚动。第一次,这些生物力学响应是通过调整肽-选择素相互作用的结合动力学来实现的。工程化MSC在E-选择素上的滚动是由Ca 2+非依赖性相互作用介导的,这是一种不同于Ca 2+依赖性生理过程的机制。这进一步说明了该方法操纵细胞-微环境相互作用的能力,特别是用于将细胞递送至靶组织的应用。它还提供了一个新的平台来设计具有多种功能的细胞。
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 Ca2+ independent interaction, a mechanism that differs from the Ca2+ 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.
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