当前位置:
X-MOL 学术
›
Nat. Commun.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Long-term functional and structural preservation of precision-cut human myocardium under continuous electromechanical stimulation in vitro.
Nature Communications ( IF 14.7 ) Pub Date : 2019-Jan-10 , DOI: 10.1038/s41467-018-08003-1 Carola Fischer , Hendrik Milting , Evelyn Fein , Elisabeth Reiser , Kun Lu , Thomas Seidel , Camilla Schinner , Thomas Schwarzmayr , Rene Schramm , Roland Tomasi , Britta Husse , Xiaochun Cao-Ehlker , Ulrich Pohl , Andreas Dendorfer
Nature Communications ( IF 14.7 ) Pub Date : 2019-Jan-10 , DOI: 10.1038/s41467-018-08003-1 Carola Fischer , Hendrik Milting , Evelyn Fein , Elisabeth Reiser , Kun Lu , Thomas Seidel , Camilla Schinner , Thomas Schwarzmayr , Rene Schramm , Roland Tomasi , Britta Husse , Xiaochun Cao-Ehlker , Ulrich Pohl , Andreas Dendorfer
In vitro models incorporating the complexity and function of adult human tissues are highly desired for translational research. Whilst vital slices of human myocardium approach these demands, their rapid degeneration in tissue culture precludes long-term experimentation. Here, we report preservation of structure and performance of human myocardium under conditions of physiological preload, compliance, and continuous excitation. In biomimetic culture, tissue slices prepared from explanted failing human hearts attain a stable state of contractility that can be monitored for up to 4 months or 2000000 beats in vitro. Cultured myocardium undergoes particular alterations in biomechanics, structure, and mRNA expression. The suitability of the model for drug safety evaluation is exemplified by repeated assessment of refractory period that permits sensitive analysis of repolarization impairment induced by the multimodal hERG-inhibitor pentamidine. Biomimetic tissue culture will provide new opportunities to study drug targets, gene functions, and cellular plasticity in adult human myocardium.
中文翻译:
在体外连续机电刺激下,精确切割的人心肌的长期功能和结构保存。
转化研究非常需要包含成年人类组织的复杂性和功能的体外模型。尽管人类心肌的重要切片满足了这些要求,但它们在组织培养中的快速变性阻碍了长期实验。在这里,我们报告在生理预紧力,依从性和连续激发条件下保存人类心肌的结构和性能。在仿生培养中,由植入的衰竭人心脏制备的组织切片达到稳定的收缩状态,可以在体外监测长达4个月或2000000次的搏动。培养的心肌在生物力学,结构和mRNA表达上经历了特定的变化。该模型对药物安全性评估的适用性通过对不应期的重复评估得到了证明,该允许期允许对多模式hERG抑制剂喷他idine诱导的复极化损伤进行敏感分析。仿生组织培养将为研究成年人类心肌中的药物靶标,基因功能和细胞可塑性提供新的机会。
更新日期:2019-01-10
中文翻译:
在体外连续机电刺激下,精确切割的人心肌的长期功能和结构保存。
转化研究非常需要包含成年人类组织的复杂性和功能的体外模型。尽管人类心肌的重要切片满足了这些要求,但它们在组织培养中的快速变性阻碍了长期实验。在这里,我们报告在生理预紧力,依从性和连续激发条件下保存人类心肌的结构和性能。在仿生培养中,由植入的衰竭人心脏制备的组织切片达到稳定的收缩状态,可以在体外监测长达4个月或2000000次的搏动。培养的心肌在生物力学,结构和mRNA表达上经历了特定的变化。该模型对药物安全性评估的适用性通过对不应期的重复评估得到了证明,该允许期允许对多模式hERG抑制剂喷他idine诱导的复极化损伤进行敏感分析。仿生组织培养将为研究成年人类心肌中的药物靶标,基因功能和细胞可塑性提供新的机会。