无支架生物正交组装三维心脏组织通过细胞表面工程。

Scaffold Free Bio-orthogonal Assembly of 3-Dimensional Cardiac Tissue via Cell Surface Engineering.

机构信息

Department of Chemistry and Biology, York University, Toronto, M3J 1P3, Canada.

OrganoLinX Inc. Toronto, Canada.

出版信息

Sci Rep. 2016 Dec 23;6:39806. doi: 10.1038/srep39806.

Abstract

There has been tremendous interest in constructing in vitro cardiac tissue for a range of fundamental studies of cardiac development and disease and as a commercial system to evaluate therapeutic drug discovery prioritization and toxicity. Although there has been progress towards studying 2-dimensional cardiac function in vitro, there remain challenging obstacles to generate rapid and efficient scaffold-free 3-dimensional multiple cell type co-culture cardiac tissue models. Herein, we develop a programmed rapid self-assembly strategy to induce specific and stable cell-cell contacts among multiple cell types found in heart tissue to generate 3D tissues through cell-surface engineering based on liposome delivery and fusion to display bio-orthogonal functional groups from cell membranes. We generate, for the first time, a scaffold free and stable self assembled 3 cell line co-culture 3D cardiac tissue model by assembling cardiomyocytes, endothelial cells and cardiac fibroblast cells via a rapid inter-cell click ligation process. We compare and analyze the function of the 3D cardiac tissue chips with 2D co-culture monolayers by assessing cardiac specific markers, electromechanical cell coupling, beating rates and evaluating drug toxicity.

摘要

人们对构建用于心脏发育和疾病的基础研究以及作为评估治疗药物发现优先级和毒性的商业系统的体外心脏组织产生了浓厚的兴趣。尽管在研究二维心脏功能方面已经取得了进展,但仍然存在难以克服的障碍,难以生成快速有效的无支架三维多细胞类型共培养心脏组织模型。在这里,我们开发了一种程序化的快速自组装策略,通过基于脂质体递送和融合以展示细胞膜上的生物正交功能基团的细胞表面工程,在心脏组织中发现的多种细胞类型之间诱导特定且稳定的细胞-细胞接触,从而生成 3D 组织。我们首次通过快速的细胞间点击连接过程,组装心肌细胞、内皮细胞和心脏成纤维细胞,生成无支架且稳定的自组装 3 细胞系共培养 3D 心脏组织模型。我们通过评估心脏特异性标志物、机电细胞偶联、跳动率和评估药物毒性,比较和分析 3D 心脏组织芯片与 2D 共培养单层的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1594/5180231/368a7cb8bc6e/srep39806-f1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索