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用于创建活体抗血栓涂层的带血源性内皮细胞的床旁快速接种心室辅助装置

Point-of-Care Rapid-Seeding Ventricular Assist Device with Blood-Derived Endothelial Cells to Create a Living Antithrombotic Coating.

作者信息

Noviani Maria, Jamiolkowski Ryan M, Grenet Justin E, Lin Qiuyu, Carlon Tim A, Qi Le, Jantzen Alexandra E, Milano Carmelo A, Truskey George A, Achneck Hardean E

机构信息

From the *Department of Surgery, Duke University Medical Center, Durham, North Carolina; †Cardiovascular & Metabolic Disorders Program, Duke - National University of Singapore Graduate Medical School, Singapore; ‡Department of Biomedical Engineering, Duke University, Durham, North Carolina; §Department of Pathology, Duke University Medical Center, Durham, North Carolina; ¶Hemostemix Inc., Toronto, Ontario, Canada; and ‖Hemostemix Inc., Ness Ziona, Israel.

出版信息

ASAIO J. 2016 Jul-Aug;62(4):447-53. doi: 10.1097/MAT.0000000000000351.

Abstract

The most promising alternatives to heart transplantation are left ventricular assist devices and artificial hearts; however, their use has been limited by thrombotic complications. To reduce these, sintered titanium (Ti) surfaces were developed, but thrombosis still occurs in approximately 7.5% of patients. We have invented a rapid-seeding technology to minimize the risk of thrombosis by rapid endothelialization of sintered Ti with human cord blood-derived endothelial cells (hCB-ECs). Human cord blood-derived endothelial cells were seeded within minutes onto sintered Ti and exposed to thrombosis-prone low fluid flow shear stresses. The hCB-ECs adhered and formed a confluent endothelial monolayer on sintered Ti. The exposure of sintered Ti to 4.4 dynes/cm for 20 hr immediately after rapid seeding resulted in approximately 70% cell adherence. The cell adherence was not significantly increased by additional ex vivo static culture of rapid-seeded sintered Ti before flow exposure. In addition, adherent hCB-ECs remained functional on sintered Ti, as indicated by flow-induced increase in nitric oxide secretion and reduction in platelet adhesion. After 15 day ex vivo static culture, the adherent hCB-ECs remained metabolically active, expressed endothelial cell functional marker thrombomodulin, and reduced platelet adhesion. In conclusion, our results demonstrate the feasibility of rapid-seeding sintered Ti with blood-derived hCB-ECs to generate a living antithrombotic surface.

摘要

心脏移植最有前景的替代方案是左心室辅助装置和人工心脏;然而,它们的使用受到血栓形成并发症的限制。为了减少这些并发症,人们开发了烧结钛(Ti)表面,但仍有大约7.5%的患者会发生血栓形成。我们发明了一种快速接种技术,通过用人脐血来源的内皮细胞(hCB-ECs)使烧结钛快速内皮化,以将血栓形成风险降至最低。人脐血来源的内皮细胞在数分钟内接种到烧结钛上,并暴露于易发生血栓形成的低流体流动剪切应力下。hCB-ECs在烧结钛上黏附并形成融合的内皮单层。快速接种后立即将烧结钛暴露于4.4达因/平方厘米的剪切应力下20小时,导致约70%的细胞黏附。在流动暴露前,对快速接种的烧结钛进行额外的体外静态培养,细胞黏附并未显著增加。此外,如流动诱导的一氧化氮分泌增加和血小板黏附减少所示,黏附在烧结钛上的hCB-ECs仍保持功能。在体外静态培养15天后,黏附的hCB-ECs仍保持代谢活性,表达内皮细胞功能标志物血栓调节蛋白,并减少血小板黏附。总之,我们的结果证明了用血液来源的hCB-ECs快速接种烧结钛以生成具有抗血栓形成功能的活性表面的可行性。

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