Tracking Human Cardiac Subtype Specification Using Molecular Beacons

使用分子信标跟踪人类心脏亚型规范

• 批准号: 8664914
• 负责人: Chunhui Xu
• 金额: $ 18.79万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8664914
• 关键词: Action Potentials; Aging; Arrhythmia; Biological Assay; Biological Pacemakers; Cardiac; Cardiac Myocytes; Cause of Death; Cell Therapy; Cell model; Cells; Characteristics; Clinic; Congenital Heart Defects; Detection; Development; Disease; Electrophysiology (science); Flow Cytometry; Fluorescence; Future; Gene Expression; Genes; Goals; Growth Factor; Heart Atrium; Heart failure; Human; Image Cytometry; In Vitro; Investigation; Ischemia; Label; Laboratories; Life; Measurement; Measures; Messenger RNA; Methods; Molecular; Myocardial; Myocardium; Nanotechnology; Natural regeneration; Nodal; Oligonucleotide Probes; Pacemakers; Patch-Clamp Techniques; Phenotype; Pluripotent Stem Cells; Population; Property; Protocols documentation; Regulation; Research; Risk; Sensitivity and Specificity; Signal Pathway; Signal Transduction; Source; Specificity; System; Technology; Time; Tissues; Transplantation; United States; Ventricular; Work; base; cardiac regeneration; cell growth; cell type; design; fluorescence imaging; gap junction channel; genetically modified cells; heart cell; injured; novel; public health relevance; regenerative; repaired; research study; tool

DESCRIPTION (provided by applicant): Human cardiac tissues have limited regenerative capacity. Damage in cardiac tissues from ischemia or other pathological conditions can result in heart failure, the leading cause of death in the United States. In addition, cell loss or dysfunctin in pacemaker tissues due to congenital heart defects, aging, and acquired diseases that damage the conduction system can cause severe arrhythmias. Human pluripotent stem cells hold great promise for cardiac cell therapy. These cells can be differentiated into nodal and working (atrial and ventricular) cardiac subtypes, which are suitable for different applications: enriched working-type cells without the contamination of nodal-type cells for repairing injured ventricular myocardium, and enriched nodal-type cells for developing a biological pacemaker. However, none of the existing methods can generate homogeneous cells for a specific subtype, and methods for the isolation and enrichment of each subtype have not been well developed. Research on cardiac subtype specification has been challenging due to the lack of an analysis tool that can be used in a throughput platform to distinguish and enrich cardiac subtypes. This R21 proposal aims to track, enrich and characterize cardiac subtypes using a novel nanotechnology based tool without genetically modifying the cells. This technology will allow us to generate highly homogeneous nodal- or working-type cell populations and therefore facilitate future applications of human pluripotent stem cells in cardiac cell therapy. It can also help accelerate studies to understand the regulation of cardiac subtype specification from human pluripotent stem cells.

描述（由申请人提供）：人类心脏组织的再生能力有限。缺血或其他病理状况导致的心脏组织损伤可能导致心力衰竭，这是美国的主要原因。此外，由于先天性心脏缺陷、衰老和损害传导系统的后天性疾病导致起搏器组织中的细胞丢失或功能障碍，可导致严重的心律失常。人类多能干细胞在心脏细胞治疗方面具有广阔的前景。这些细胞可以分化为结型和工作（心房和心室）心脏亚型，适合不同的应用：富集的工作型细胞，没有受到结型细胞的污染，用于修复受损的心室心肌；富集的结型细胞，用于修复受损的心室心肌。开发生物起搏器。然而，现有的方法都不能产生特定亚型的同质细胞，并且分离和富集每种亚型的方法尚未得到很好的开发。由于缺乏可在通量平台中用于区分和丰富心脏亚型的分析工具，对心脏亚型规范的研究一直具有挑战性。该 R21 提案旨在使用基于纳米技术的新型工具来跟踪、丰富和表征心脏亚型，而无需对细胞进行基因改造。这项技术将使我们能够产生高度同质的节点型或工作型细胞群，从而促进人类多能干细胞在心脏细胞治疗中的未来应用。它还可以帮助加速研究，以了解人类多能干细胞对心脏亚型规范的调节。

项目成果

In vitro organogenesis from pluripotent stem cells.

多能干细胞的体外器官发生。

• 发表时间: 2014-04
• 影响因子: 2.3
• 作者: Li, Yan;Xu, Chunhui;Ma, Teng
• 通讯作者: Ma, Teng

Cell alignment induced by anisotropic electrospun fibrous scaffolds alone has limited effect on cardiomyocyte maturation.

单独由各向异性电纺纤维支架诱导的细胞排列对心肌细胞成熟的影响有限。

• 发表时间: 2016-05
• 影响因子: 1.2
• 作者: Han, Jingjia;Wu, Qingling;Xia, Younan;Wagner, Mary B;Xu, Chunhui
• 通讯作者: Xu, Chunhui

Efficient differentiation of cardiomyocytes from human pluripotent stem cells with growth factors.

使用生长因子从人多能干细胞中有效分化心肌细胞。

• DOI: 10.1007/978-1-4939-2572-8_9
• 发表时间: 2015
• 期刊: Methods in molecular biology
• 作者: Jha R;Xu RH;Xu C
• 通讯作者: Xu C

Microscale generation of cardiospheres promotes robust enrichment of cardiomyocytes derived from human pluripotent stem cells.

心肌球的微尺度生成促进了源自人类多能干细胞的心肌细胞的强劲富集。

• 发表时间: 2014-08-12
• 影响因子: 5.9
• 作者: Nguyen, Doan C;Hookway, Tracy A;Wu, Qingling;Jha, Rajneesh;Preininger, Marcela K;Chen, Xuemin;Easley, Charles A;Spearman, Paul;Deshpande, Shriprasad R;Maher, Kevin;Wagner, Mary B;McDevitt, Todd C;Xu, Chunhui
• 通讯作者: Xu, Chunhui

Molecular beacon-based detection and isolation of working-type cardiomyocytes derived from human pluripotent stem cells.

基于分子信标的人类多能干细胞来源的工作型心肌细胞的检测和分离。

• DOI: 10.1016/j.biomaterials.2015.01.043
• 发表时间: 2015-05
• 期刊: Biomaterials
• 影响因子: 14
• 作者: Jha, Rajneesh;Wile, Brian;Wu, Qingling;Morris, Aaron H.;Maher, Kevin O.;Wagner, Mary B.;Bao, Gang;Xu, Chunhui
• 通讯作者: Xu, Chunhui