Trends and Limitations in the Assessment of the Contractile Properties of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes From Patients With Dilated Cardiomyopathy
Trends and Limitations in the Assessment of the Contractile Properties of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes From Patients With Dilated Cardiomyopathy
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DOI：
10.3389/fcvm.2020.00154
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发表时间：
2020-09-03
影响因子：
3.6
通讯作者：
Komuro, Issei
中科院分区：
文献类型：
--
作者：
Ito, Masamichi;Nomura, Seitaro;Komuro, Issei
人诱导多能干细胞来源的心肌细胞（hiPSCMs）有望在体外疾病建模和药物筛选中得到应用。扩张型心肌病（DCM）是一种以收缩功能受损为特征的顽固性疾病，可导致严重的心力衰竭。许多研究人员专注于DCM的疾病建模，并在hiPSCM中复制其病理表型，但评价体外心肌细胞收缩特性的可靠方法尚未标准化。此外，尚不清楚测量和分析的通量是否可以充分增加以用于化合物筛选。在这里，我们回顾了文章中的DCM hiPSCM的收缩异常进行了概括，并评估了样品制备和评价的趋势和问题。我们发现，单细胞水平的分析是无效的，在某些情况下，和组织工程的方法已成为主导，最近，因为它的效率增加再生受损的收缩性。我们还研究了两种市售的自动测量设备，具有中等的吞吐量，用于使用由最初建立的DCM hiPSCM组成的二维hiPSCM片进行运动分析。因此，两种测试设备（阻抗分析仪和基于视频图像的细胞运动分析仪）都无法有效检测DCM克隆中预期的收缩力降低。这些研究结果共同表明，组织工程方法可以扩大hiPSCM疾病建模的潜力，到目前为止，具有足够通量但不牺牲生理保真度的体外力测量的适当方法正在等待。
The application of human induced pluripotent stem cell-derived cardiomyocytes (hiPSCMs) from patients is expected in disease modeling and drug screeningin vitro. Dilated cardiomyopathy (DCM) is an intractable disease characterized by the impairment of systolic function and leads to severe heart failure. A number of researchers have focused on disease modeling of DCM and reproduced its pathologic phenotypes in hiPSCMs, but a robust method to evaluate the contractile properties of cardiomyocytesin vitrohas not been standardized. In addition, it is unknown whether the throughput of measurements and analyses could be increased sufficiently for compound screening. Here, we reviewed the articles in which the contractile abnormalities of DCM hiPSCMs were recapitulated and assessed the trends and problems in sample preparation and evaluation. We found that single-cell level analysis was ineffective in some cases, and a tissue engineering approach has become dominant recently because of its increased efficiency in reproducing impaired contractility. We also examined two commercially available automated measurement devices with moderate throughput for motion analysis using two-dimensional hiPSCM sheets composed of originally established DCM hiPSCMs. As a result, both of the tested devices, an impedance analyzer and a video image-based cell motion analyzer, were not effective in detecting the expected reduction of contractility in the DCM clone. These findings collectively suggest that a tissue engineering approach could expand the potential of disease modeling with hiPSCMs, and so far, appropriate methods forin vitroforce measurement with sufficient throughput, but without sacrificing physiological fidelity, are awaited.