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Targeted repair of heart injury by stem cells fused with platelet nanovesicles.
Nature Biomedical Engineering ( IF 28.1 ) Pub Date : 2018-01-10 , DOI: 10.1038/s41551-017-0182-x
Junnan Tang 1, 2, 3 , Teng Su 1, 2 , Ke Huang 1 , Phuong-Uyen Dinh 1 , Zegen Wang 4 , Adam Vandergriff 1, 2 , Michael T Hensley 1, 2 , Jhon Cores 1, 2 , Tyler Allen 1 , Taosheng Li 5 , Erin Sproul 2 , Emily Mihalko 2 , Leonard J Lobo 6 , Laura Ruterbories 7 , Alex Lynch 7 , Ashley Brown 2 , Thomas G Caranasos 8 , Deliang Shen 1, 2, 3 , George A Stouffer 9 , Zhen Gu 2 , Jinying Zhang 3 , Ke Cheng 1, 2, 4, 10
Affiliation  

Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types.



中文翻译:

融合有血小板纳米囊泡的干细胞靶向修复心脏损伤。

临床上使用的干细胞移植遭受移植细胞的保留和植入率低的困扰。受血小板将干细胞募集到血管损伤部位的能力的启发,我们假设血小板可能会增强心脏干细胞(CSC)向心肌梗塞损伤部位的血管输送。在这里,我们显示具有融合在其表面膜上的血小板纳米囊泡的CSCs表达与血小板粘附至损伤部位相关的血小板表面标志物。我们还发现,修饰的CSCs选择性结合胶原蛋白包被的表面和内皮剥落的大鼠主动脉,并且在急性心肌梗死的大鼠和猪模型中,修饰的CSCs增加了心脏的保留并减小​​了梗塞面积。因此,融合血小板的新鼻祖细胞具有其亲代细胞类型的天然靶向和修复能力。这种干细胞操作方法是快速,直接和安全的,不需要对细胞进行遗传改造,并且应可推广到多种细胞类型。

更新日期:2018-01-11
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