Univ. Bordeaux, Chimie et Biologie des Membranes et Nano-Objets (UMR5248 CBMN), Pessac, France.
CNRS, CBMN UMR5248, Pessac, France.
J Biomed Mater Res A. 2020 May;108(7):1479-1492. doi: 10.1002/jbm.a.36918. Epub 2020 Apr 16.
Synthetic grafts do not provide an appealing surface for endothelial cells to adhere and colonize the inner surface. To promote in situ endothelialization the following aspect has to be taken into account, endothelial progenitor cells (EPCs) needs to be mobilized on the surface of the graft. The surface of the graft has to be sufficiently biocompatible to create a prone environment for the EPCs to adhere, proliferate and, differentiate to form a layer and subsequently improve graft patency. In this work, two active molecules GRGDS and sitagliptin, were chosen for their abilities to recruit, enhance adhesion and induce differentiation of endothelial progenitor cells. They were grafted on PET surfaces in order to provide restrained cues triggering cell alignment and evaluate the influence of such structuration on EPCs fate. We then analyze cell behavior onto functionalized biomaterials. Their abilities to control EPCs fate were demonstrated via RT-qPCR, immunofluorescence, and enzymatic tests. The GRGDS/sitagliptin 100 × 10 surface enables to reduce the stemness phenotype on EPCs and induce the expression of endothelial lineage markers. These results highlight the importance of spatial patterning cues in guiding EPCs organization and function, which may have clinical relevance in the development of vascular grafts that promote patency.
合成移植物不能为内皮细胞提供一个理想的附着和定殖内表面的表面。为了促进原位内皮化，必须考虑以下方面，需要动员移植物表面的内皮祖细胞 (EPC)。移植物的表面必须具有足够的生物相容性，以创造一个有利于 EPC 附着、增殖和分化形成一层的环境，从而提高移植物的通畅性。在这项工作中，选择了两种活性分子 GRGDS 和西他列汀，因为它们具有招募、增强 EPC 粘附和诱导分化的能力。将它们接枝到 PET 表面上，以提供限制细胞排列的线索，并评估这种结构对 EPCs 命运的影响。然后，我们分析了细胞在功能化生物材料上的行为。通过 RT-qPCR、免疫荧光和酶试验证明了它们控制 EPCs 命运的能力。GRGDS/sitagliptin 100×10 表面能够降低 EPC 的干性表型，并诱导内皮谱系标志物的表达。这些结果强调了空间图案线索在指导 EPCs 组织和功能方面的重要性，这在开发促进通畅性的血管移植物方面可能具有临床意义。
