Biomimetic material strategies for cardiac tissue engineering

Cardiovascular disease precedes many serious complications including myocardial infarction (MI) and it remains a major problem for the global community. Adult mammalian heart has limited ability to regenerate and compensate for the loss of cardiomyocytes. Restoration of cardiac function by replacement of diseased myocardium with functional cardiomyocytes is an intriguing strategy because it offers a potential cure for MI. Biomaterials are fabricated in nanometer scale dimensions by combining the chemical, biological, mechanical and electrical aspects of material for potential tissue engineering (TE) applications. Synthetic polymers offer advantageous in their ability to tailor the mechanical properties, and natural polymers offer cell recognition sites necessary for cell, adhesion and proliferation. Cardiac tissue engineering (TE) aim for the development of a bioengineered construct that can provide physical support to the damaged cardiac tissue by replacing certain functions of the damaged extracellular matrix and prevent adverse cardiac remodeling and dysfunction after MI. Electrospun nanofibers are applied as heart muscle patches, while hydrogels serve as a platform for controlled delivery of growth factors, prevent mechanical complications and assist in cell recruitment. This article reviews the applications of different natural and synthetic polymeric materials utilized as cardiac patches, injectables or 3D constructs for cardiac TE. Smart organization of nanoscale assemblies with synergistic approaches of utilizing nanofibers and hydrogels could further advance the field of cardiac tissue engineering. Rapid innovations in biomedical engineering and cell biology will bring about new insights in the development of optimal scaffolds and methods to create tissue constructs with relevant contractile properties and electrical integration to replace or substitute the diseased myocardium.     

ERK信号转导通路在心肌缺血再灌注损伤中的作用

细胞外信号调节激酶(ERK1/2)作为丝裂原活化蛋白激酶家族中一个重要的亚族,在调节细胞的生长、分化、应激以及死亡中起重要作用。大量研究表明,ERK信号通路在体内外心肌缺血/再灌注损伤过程中被激活并发挥了重要作用。激活ERK既可以促进细胞存活,也可以介导细胞损伤,这与细胞种类的不同或缺血/再灌注的程度及时程的不同有关。本文就ERK信号转导通路在心肌缺血再灌注损伤中的作用及其机制作一综述。     

Design of large-scale manufacturing of induced pluripotent stem cell derived cardiomyocytes

A new approach for design of large-scale manufacture of stem cell derived cells by using the biomechatronic methodology and computer-aided-design tools is described. The systematic conceptual design methodology for systems composed of active mechanical, electronic and biological components, here referred to as biomechatronics, is combined with the methodology for computer-aided design of bioprocesses. The objective has been to systematically investigate and compare by the combination of the methodologies what are favourable design alternatives in terms of equipment configuration and economic parameters. A demonstration case has been used for the manufacture of cardiomyocytes from human induced pluripotent stem cells. The results show how certain configurations are more favourable than others under given boundary conditions. The study indicates that the approach is possible to apply on other related bio-manufacturing systems.     

珠子参总皂苷对H2O2诱导新生大鼠心肌细胞凋亡的抑制作用

目的: 观察珠子参总皂苷对H₂O₂诱导新生大鼠心肌细胞凋亡的抑制作用,并探讨其作用机制。方法: Wistar乳鼠心肌细胞原代培养,用H₂O₂建立氧化应激损伤模型,然后用珠子参总皂苷(100, 200 μg/mL)孵育 24 h后,MTT法检测珠子参总皂苷对细胞活力的影响,流式细胞仪和Hoechst33258染色检测珠子参总皂苷对氧化应激诱导细胞凋亡及胞内ROS含量的影响,比色法测定心肌细胞Caspase-3、Caspase-9的活性,荧光定量PCR测定心肌细胞Bcl-2和Bax mRNA表达,并计算Bcl-2与Bax的比值。结果: 珠子参总皂苷(100, 200 μg/mL)能显著改善心肌细胞活性,有效保护线粒体膜电位的稳定,抑制心肌细胞凋亡和改善细胞形态,降低细胞内活性氧(ROS)含量;下调Bax mRNA表达,上调Bcl-2 mRNA表达及Bcl-2与Bax的比值;降低H₂O₂所致新生大鼠心肌细胞中Caspase-3、Caspase-9的活性。结论: 珠子参总皂苷对H₂O₂诱导心肌细胞凋亡有显著的抑制作用,其机制可能与其稳定心肌细胞膜、清除ROS及调节心肌细胞Bcl-2、Bax和Caspase-3、Caspase-9表达有关。     

A multi-scale electrode array (MSEA) to study excitation-contraction coupling of cardiomyocytes for high-throughput bioassays

Excitation-contraction coupling, a process of linking electrical activity to contraction, is the basis of cardiac function at cellular level. Here we developed a multi-scale electrode array (MSEA) as an in vitro platform to synchronously monitor excitation and contraction of cultured cardiomyocytes. The electrodes of MSEA were with sizes ranging from several tens of micrometers to about 1 mm and were classified into type_1, type_2 and type_3 by their electrode area. The former two types of electrodes were electroplated with platinum black to reduce baseline noise and no extra treatment was done on type_3 electrodes. In experiment, the micrometer-scale electrodes recorded extracellular field potentials like generally used multielectrode arrays and especially, the millimeter-scale electrodes recorded a “hump” followed after extracellular field potential. By analyzing temporal behavior of hump and observing its change under treatment of microtubule inhibitor vinblastine, it was verified that the hump expressed mechanical contraction of cardiomyocytes. In addition, we analyzed that the pathway of contraction recording was through cell-electrode contractile coupling, in which charges at electrode-electrolyte interface were reestablished due to contractile behavior of cellular layer and then the hump was formed. Finally, the dependence of amplitude and time duration of hump on electrode area, electrode property and contractile strength was also explored.     

活性氧物质在多柔比星诱导的心肌细胞凋亡中的作用

目的观察活性氧物质(Reactive oxygen species,ROS)在多柔比星(Doxorubicin,Dox)诱导的心肌细胞凋亡中的作用。方法将大鼠胚胎期心肌细胞H9C2分为对照组、Dox 0.1μmol/L组和Dox 1.0μmol/L组,Dox作用24 h后,采用硫代巴比妥酸(Thibatituric acid,TBA)法检测丙二醛(Malondialchehyche,MDA)含量;血浆三价铁降低能力法(Ferric reducing ability of plasma,FRAP)检测总抗氧化能力(Total antioxidation capability,T-AOC);DCFH-DA荧光探针染色法检测ROS含量;JC-1染色法检测线粒体膜电位(Mitochondrial membrane potential,△ψm);TUNEL法检测心肌细胞凋亡指数(AI)。结果与对照组相比,DOX 1.0μmol/L组MDA、ROS含量及AI显著上升(P<0.05),T-AOC及△ψm显著下降(P<0.05)。结论 Dox诱导心肌细胞凋亡过程中,ROS生成增加,超过了抗氧化体系的清除能力,氧化应激损伤机制发挥了重要作用。