Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration.
Glycosyltransferase-programmed stereosubstitution (GPS) to create HCELL: engineering a roadmap for cell migration.
复制标题
DOI：
10.1111/j.1600-065x.2009.00792.x
复制
发表时间：
2009-07
影响因子：
8.7
通讯作者：
Sackstein R
中科院分区：
文献类型：
--
作者：
Sackstein R
在脊椎动物心血管系统的进化过程中，与分支血管网络相关的巨大内皮表面积要求分子过程的发展，以在炎症/组织损伤的局部位点有效和特异性地招募循环前哨宿主防御细胞和组织修复细胞。由高速血流产生的力必然需要能够介导抗剪切内皮粘附相互作用的特化细胞表面分子的进化，从而字面上将血流中的相关细胞捕获到目标内皮表面上并允许随后的外渗。这些抗剪切结合相互作用的主要效应物包括称为“选择素”的C型凝集素家族，其结合其各自配体上的离散唾液酸岩藻糖基化聚糖。这篇综述解释了必要的试剂的“智能设计”，以将天然CD 44转化为称为造血细胞E-/L-选择素配体（HCELL）的唾液酸岩藻糖基化糖型，HCELL是人类细胞上表达的最有效的E-选择素反受体，并将描述HCELL表达的离体聚糖工程如何为各种细胞疗法的有效血管递送细胞开辟“途径”。
During evolution of the vertebrate cardiovascular system, the vast endothelial surface area associated with branching vascular networks mandated the development of molecular processes to efficiently and specifically recruit circulating sentinel host defense cells and tissue repair cells at localized sites of inflammation/tissue injury. The forces engendered by high-velocity blood flow commensurately required the evolution of specialized cell surface molecules capable of mediating shear-resistant endothelial adhesive interactions, thus literally capturing relevant cells from the blood stream onto the target endothelial surface and permitting subsequent extravasation. The principal effectors of these shear-resistant binding interactions comprise a family of C-type lectins known as ‘selectins’ that bind discrete sialofucosylated glycans on their respective ligands. This review explains the ‘intelligent design’ of requisite reagents to convert native CD44 into the sialofucosylated glycoform known as hematopoietic cell E-/L-selectin ligand (HCELL), the most potent E-selectin counter-receptor expressed on human cells, and will describe how ex vivo glycan engineering of HCELL expression may open the ‘avenues’ for the efficient vascular delivery of cells for a variety of cell therapies.