2012-Directed Differentiation of Stem Cells to Cardiomyocytes Using Optically Act

2012-利用光学作用将干细胞定向分化为心肌细胞

• 批准号: 8444918
• 负责人: Anastasios John Hart
• 金额: $ 19.95万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8444918
• 关键词: Affect; Area; Benchmarking; Biological Assay; Calibration; Calorimetry; Carbon Nanotubes; Cardiac; Cardiac Myocytes; Cell Culture Techniques; Cell Survival; Cell physiology; Cells; Chemicals; Custom; Development; Dimensions; Disease; Elastomers; Engineering; Environment; Frequencies; Gene Proteins; Genes; Glass; Goals; Growth; Heart; Image; Individual; Lateral; Libraries; Lighting; Literature; Measures; Mechanical Stimulation; Mechanics; Microfilaments; Microscope; Microscopy; Modeling; Molds; Natural regeneration; Optics; Pathology; Pathway interactions; Performance; Polymers; Property; Research; Shapes; Signal Transduction; Silicon; Speed; Spottings; Stem cells; Stretching; Structure; Surface; System; Technology; Testing; Time; Tissues; Work; azobenzene; base; cardiogenesis; cell behavior; cell type; design; high throughput analysis; high throughput screening; human embryonic stem cell; improved; instrument; liquid crystal; magnetic field; new technology; novel; poly(dimethylsiloxane); public health relevance; research study; stem cell differentiation; tool

DESCRIPTION (provided by applicant): We propose a new technology for dynamic stem cell culture, using arrays of optically actuated polymer microposts. The polymer structures will be created by replica molding of straight and slanted microposts, made using carbon nanotube (CNT) and silicon master molds. The replica structures will be cast using photoactive liquid crystal elastomers (LCEs). Illumination of the LCE microposts will cause a rapid change in their shape and/or stiffness; and it will be possible to actuate arbitrary areas of posts based on the spot size and intensity of the illumination beam. We will assess cell viability on LCE structures i comparison to conventional poly- dimethylsiloxane (PDMS) structures as a benchmark material, by engineering the geometry and stiffness of the two materials. Using designed arrays of microposts enabling dynamic modulation of rigidity and strain that mimics the amplitude and force of cardiomyocyte beating, we will investigate pathways for mechanically-modulated differentiation of human embryonic stem cells (hESCs) into cardiomyocytes. Thus, we will aim to improve the accuracy and throughput of cardiomyocyte differentiation, and the understanding of how mechanotransduction affects cardiogenic differentiation. Successful development of this novel system would enable further research on mechanotransductive signaling under dynamic control, and possibly the realization of mechanically controlled assays for high-throughput cell culture. 1

描述（由申请人提供）：我们提出了一种新的技术，用于动态干细胞培养，使用阵列的光学驱动聚合物微柱。聚合物结构将通过直的和倾斜的微柱的复制品成型来创建，这些微柱使用碳纳米管（CNT）和硅母模制成。复制品结构将使用光敏液晶弹性体（LCE）铸造。LCE微柱的照明将导致其形状和/或刚度的快速变化;并且将有可能基于照明光束的光斑尺寸和强度来致动柱的任意区域。我们将通过设计两种材料的几何形状和刚度，与作为基准材料的常规聚二甲基硅氧烷（PDMS）结构相比，评估LCE结构上的细胞活力。使用设计的微柱阵列，能够动态调节刚度和应变，模仿心肌细胞跳动的幅度和力量，我们将研究人类胚胎干细胞（hESC）的机械调节分化为心肌细胞的途径。因此，我们将致力于提高心肌细胞分化的准确性和通量，以及对机械转导如何影响心源性分化的理解。这种新系统的成功开发将使进一步研究动态控制下的机械转导信号，并可能实现高通量细胞培养的机械控制测定。1