Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform

Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~ 30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel

Performance Evaluation of CWH Base Isolated Building During Two Major Earthquakes in Christchurch

The seismic performance and parameter identification of the base isolated Christchurch Women’s Hospital (CWH) building are investigated using the recorded seismic accelerations during the two large earthquakes in Christchurch. A four degrees of freedom shear model is applied to characterize the dynamic behaviour of the CWH building during these earthquakes. A modified Gauss-Newton method is employed to identify the equivalent stiffness and Rayleigh damping coefficients of the building. The identification method is first validated using a simulated example structure and finally applied to the CWH building using recorded measurements from the Mw 6.0 and Mw 5.8 Christchurch earthquakes on December 23, 2011. The estimated response and recorded response for both earthquakes are compared with the cross correlation coefficients and the mean absolute percentage errors reported. The results indicate that the dynamic behaviour of the superstructure and base isolator was essentially within elastic range and the proposed shear linear model is sufficient for the prediction of the structural response of the CWH Hospital during these events