Advancing High-Throughput Cardiac Screening With Physiologically Relevant 3D iPSC-Based Models

Traditional 2D assays are not always physiologically relevant. Engineered heart tissues are too slow. Enter: 3D cardiac models.  

Microtissues engineered from iPSC-derived cells that recreate the structural and functional characteristics of human heart tissue, 3D cardiac models are the high-throughput solution early-stage drug screening and disease modeling require.  

 In “Advancing High-Throughput Cardiac Screening With Physiologically Relevant 3D iPSC-Based Models,” a webinar hosted by Ncardia, Mariana Argenziano, Ph.D.,  
associate director manufacturing technology at Ncardia, and Richard Davis, Ph.D.,  
assistant professor at LUMC, discuss Ncardia’s Ncyte^® Heart in a Box™ 3D cardiac model and how Ncardia helped LUMC to make serious advancements in their search for newer and better treatments for catecholaminergic polymorphic ventricular tachycardia (CPVT).  

Here’s a preview.  

Meet Ncyte^® Heart in a Box™ 

The industry has a clear need for a high-throughput 3D model suitable for early-stage drug screening and disease modeling, so Ncardia made Heart in a Box™. 

A cost-effective, scalable, physiologically relevant 3D model, Heart in a Box™ is:  

• 70% ventricular cardiomyocytes for contraction and electrical activity 
• 15% endothelial cells, providing vascular-like structures and barrier function 
• 15% cardiac fibroblasts for extracellular matrix (ECM), structural integrity and cell-cell signaling 

Because it’s designed for high-throughput cardiac screening (384-well format), Heart in a Box™ supports screening of 1,500+ data points per day. It is also functionally validated, offers automatic microtissue formation to reduce variability, increase  reproducibility and reduce time-to-data, and is aligned with the FDA’s shift away from animal testing.  

Applications of Ncyte^® Heart in a Box™ 

Heart in a Box™ has an extensive list of applications including:  

• Cardiotoxicity screening 
• Disease modeling 
• Precision medicine 
• And more  

It can capture functional responses like calcium transients, arrhythmias and beat rate changes in a format that reflects native cardiac tissue behavior. It can also be used with both Ncardia’s off-the-shelf cells and with patient-derived iPSCs for precision medicine and disease modeling. 

To put it simply: Heart in a Box™ offers multi-parametric, human-relevant data in cardiotoxicity screening, helping researchers make better decisions earlier in the pipeline. 

Case Study: Disease Modeling With LUMC

A prime example of the benefits 3D cardiac models offer is the work Ncardia did with LUMC searching for new CPVT treatments.  

With Ncardia’s help, LUMC created a screening automation pipeline that included: 

• Robotic tissue generation 
• Automated calcium imaging in 384-well format 
• Pilot screen validated with known drug (flecainide) and novel hits 

They used 3D cardiac microtissues for both arrhythmia modeling and high-throughput cardiac screening with incredible results.  

The disease phenotype (arrhythmias) was triggered in >95% of microtissues and the LUMC team was able to screen 2,000+ compounds in triplicate — with 97 hits identified that rescued the arrhythmic phenotype — in just two days.  

What Could You Accomplish With Heart in a Box™?  

3D models like Heart in a Box™ are the future of high-throughput cardiac screening. But you might be left wondering:  

• How is Heart in a Box™ functionally validated?  
• What goes into its automatic microtissue formation?  
• Are there data to support its possible applications?
• What about bioreactor challenges and quality control? Patient-specific iPSCs?  

To answer these questions and more, watch the full webinar.