首页> 外文期刊>Journal of Functional Biomaterials >Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes
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Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes

机译:模仿组织的几何约束刺激小鼠新生和人类诱导的多能干细胞衍生的心肌组织的组织结构和活性。

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The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.
机译:本工作解决了在人造心脏组织的设置中几何支撑在多大程度上充当生理确定模板的问题。具有细胞大小尺寸的交替的凹凸过渡的表面图案用于组织和定向人类诱导的多能干细胞(hIPSC)衍生的心肌细胞和小鼠新生儿心肌细胞。细胞的形状以及收缩装置的组织概括了从组织几何学动机得出的各向异性线图案几何学。检查了收缩装置的细胞内组织和经由以随机或有组织的模式生长的细胞装配体的间隙连接的细胞偶联。细胞在空间和时间上的协调激发和收缩已经在普通的和图案化的基材上进行了比较。虽然α-肌动蛋白的细胞骨架组织可与最终发育的天然心室组织相媲美,但是连接蛋白43的表达不能概括心肌组织的间隙连接分布。但是,可以观察到协调的收缩。组织样细胞集合组织的结果为依赖几何形状的细胞组织,从干细胞培养人工心脏组织以及治疗化合物的各向异性依赖性活性提供了新的见解。

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