图1通过动态训练培养获得的人iPS细胞的三维微心脏组织
(左)心肌细胞(红色)和血管壁细胞(围绕血管内皮细胞;绿色)。比例尺为200μm。
(中)血管内皮细胞(绿色)。在微心脏组织中形成血管网络。比例尺为200μm。
(右)心肌层(棕色)。微心脏组织的厚度超过150μm。
图2 MEMS技术制成的微流控芯片
中心圆(直径4毫米)在底部具有直径为2毫米的凸部,当将微型心脏置于顶部时,心跳将传递到下方的微型通道。白色箭头表示在微通道的流入侧上宽度为100μm的凹槽,荧光粒子流过该凹槽。
RIKEN:具有iPS单元的“芯片上心脏”:已开发的微型设备
理肯:
合作研究小组:
人类iPS细胞技术和
使用微设备技术,
开发了“心形[4]型微设备”。
片上心脏[4]型微设备高度灵敏地评估人心脏的功能。
研究结果:
这项研究的结果将有助于使用iPS细胞进行心脏再生医学和药物发现研究。
心脏病再生药:
在用于心脏病的再生医学和药物发现研究中,期望从人iPS细胞人工产生的三维人心脏组织的应用。
人造心脏组织的功能评估:
传统问题:
尚未建立能够以高灵敏度评估再生的人造心脏组织的功能的系统。
这项发展:
这次,联合研究小组开发了一种“片上心脏型微设备”,并建立了前所未有的高灵敏度人工心脏功能评估系统。
细胞片3D微心脏组织:
来自人类iPS细胞:
开发了通过动态训练培养增厚的细胞片状三维微心脏组织[5]。
使用微加工技术:
使用微通道的流体心功能评估系统的组合。
这项研究将发布在科学杂志“ Scientific Reports”(11月5日)的在线版本上。
理化研究所
https://www.riken.jp/press/2020/20201105_5/
Establishment of a heart-on-a-chip microdevice based on human iPS cells for the evaluation of human heart tissue function
Abstract
Human iPS cell (iPSC)-derived cardiomyocytes (CMs) hold promise for drug discovery for heart diseases and cardiac toxicity tests.
To utilize human iPSC-derived CMs,
the establishment of three-dimensional (3D) heart tissues from iPSC-derived CMs and other heart cells,and a sensitive bioassay system to depict physiological heart function are anticipated.
We have developed a heart-on-a-chip microdevice (HMD)
as a novel system consisting of dynamic culture-based 3D cardiac microtissues
derived from human iPSCs and microelectromechanical system (MEMS)-based microfluidic chips.The HMDs
could visualize the kinetics of cardiac microtissue pulsations by monitoring particle displacement,which enabled us to quantify the physiological parameters, including fluidic output, pressure, and force.
The HMDs
demonstrated a strong correlation between particle displacement and the frequency of external electrical stimulation.The transition patterns
were validated by a previously reported versatile video-based system to evaluate contractile function.The patterns
are also consistent with oscillations of intracellular calcium ion concentration of CMs, which is a fundamental biological component of CM contraction.The HMDs showed a pharmacological response to isoproterenol,
a β-adrenoceptor agonist, that resulted in a strong correlation between beating rate and particle displacement.
Thus, we have validated the basic performance of HMDs as a resource for human iPSC-based pharmacological investigations.
Scientific Reports