医学
T细胞
MXenes公司
炎症
免疫学
移植
脐静脉
心脏移植
内皮细胞活化
细胞生物学
免疫系统
癌症研究
体外
生物
材料科学
纳米技术
生物化学
内科学
作者
Weiang Yan,Alireza Rafieerad,Keshav Narayan Alagarsamy,Rakesh C. Arora,Sanjiv Dhingra
出处
期刊:Circulation
[Ovid Technologies (Wolters Kluwer)]
日期:2022-11-08
卷期号:146 (Suppl_1)
标识
DOI:10.1161/circ.146.suppl_1.15705
摘要
Introduction: Cardiac allograft vasculopathy is an aggressive form of atherosclerosis and a major cause of mortality among patients with heart transplants. Blood vessel endothelial cells stimulate alloreactive T-lymphocytes to result in sustained inflammation. MXenes are an emerging class of nanomaterials that have been shown to possess immunomodulatory properties. Herein, we report the first application of titanium carbide (Ti 3 C 2 T x ) MXene nanosheets for prevention of allograft vasculopathy. Methods and Results: Detailed physicochemical characterization of Ti 3 C 2 T x MXene nanosheets was performed using scanning/transmission electron microscopy, x-ray diffraction, and x-ray photoelectron spectroscopy. Ti 3 C 2 T x MXene nanosheets were 2 to 5 μm in size and enriched with biologically active surface groups. In vitro , MXene nanosheets interacted with human umbilical vein endothelial cells (HUVECs) and downregulated the expression of genes involved in alloantigen presentation through the class I major histocompatibility complex (IRF1, TAP1, B2M), and reduced the activation and pro-inflammatory polarization of co-cultured allogeneic lymphocytes. Consequently, RNA-Seq analysis of these lymphocytes showed that treatment with MXene nanosheets downregulated genes responsible for transplant-induced T-cell activation, cell-mediated rejection, and development of allograft vasculopathy. Furthermore, gene set enrichment analysis revealed significant negative enrichment of genes involved in interferon alpha/beta and interferon gamma signaling. Finally, in an in vivo rat model of allograft vasculopathy, treatment with Ti 3 C 2 T x MXene nanosheets reduced lymphocyte infiltration and preserved medial smooth muscle cell integrity within transplanted aortic allografts. Conclusion: These findings support the potential of Ti 3 C 2 T x MXene nanosheets for prevention and treatment of allograft vasculopathy and other inflammatory diseases. This research also opens the door to development of Ti 3 C 2 T x MXene technologies for other immune-sensitive regenerative medicine applications.
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