Wu Pei-Jung, Peng Hsuan, Li Cong, Abdel-Latif Ahmed, Berron Brad J
Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky 40506-0046, United States.
College of medicine, University of Kentucky, Lexington, Kentucky 40506-0046, United States.
ACS Appl Bio Mater. 2020 May 18;3(5):2930-2939. doi: 10.1021/acsabm.9b01198. Epub 2020 Apr 22.
Injection into the heart tissue is a direct route for optimally placing mesenchymal stem cells (MSC) to regulate local inflammation following a heart attack. The retention of MSCs at the injection site is severely limited by the fluid flows that rapidly wash cells away and minimize their capacity to modulate cardiac inflammation. To prevent this loss of MSCs and their function, antibody coatings were designed for the surface of MSCs to enhance their adhesion to the inflamed tissue. MSCs were biotinylated, and biotinylated antibodies against intercellular cell adhesion molecules were conjugated to the cell surface through an intermediate layer of streptavidin. MSC surfaces were modified with ~7,000 biotin/μm and ~23 antibodies/μm. The heart tissue injection of antibody-coated MSCs offered a 3-fold increase of cell retention in an infarcted heart over the injection of uncoated MSCs. We supported the mechanism of adhesion through analysis of MSC adhesion to inflamed endothelial cells and also surfaces of purified adhesion molecules on glass under microfluidic shear flow.
将间充质干细胞(MSC)注入心脏组织是在心脏病发作后最佳地放置这些细胞以调节局部炎症的直接途径。MSC在注射部位的留存受到严重限制,因为流体流动会迅速将细胞冲走,并使其调节心脏炎症的能力降至最低。为防止MSC及其功能的这种损失,设计了针对MSC表面的抗体涂层,以增强其对炎症组织的粘附。对MSC进行生物素化处理,并通过链霉亲和素中间层将抗细胞间粘附分子的生物素化抗体偶联到细胞表面。MSC表面修饰有每微米约7000个生物素和每微米约23个抗体。与注射未包被抗体的MSC相比,向心脏组织注射包被抗体的MSC后,梗死心脏中的细胞留存增加了3倍。我们通过分析MSC在微流体剪切流条件下对炎症内皮细胞以及玻璃上纯化粘附分子表面的粘附情况,来支持这种粘附机制。