Skip to content

Expert Insights: 3D human iPSC-based cardiac models

By Tessa de Korte, PhD candidate

Bringing 3D human iPSC-based cardiac models into early drug discovery

Tessa de Korte
Tessa de Korte,
PhD Candidate
LUMC / Ncardia
Expert Profile

Tessa de Korte holds a Master of Science in Bio-Pharmaceutical Sciences from the University of Leiden. In 2015 she joined Ncardia as an Application Specialist, where she was actively involved in R&D programs and services for drug safety and efficacy testing. In addition, she leveraged her expertise providing scientific support to partners and customers and represented Ncardia at scientific events In 2019, Tessa decided to pursue a PhD in a collaborative project between the Leiden University Medical Center (LUMC) and Ncardia, with a focus on developing high-throughput strategies to functionally evaluate new human iPSC-based models of inherited arrhythmia disorders.

Insights

The introduction of disease models based on human iPSCs has enabled bringing human biology to the early stages of drug discovery, increasing the chances of success in clinical trials. Today we talk with Tessa about the next revolution in the field of human iPSC technology: 3D cardiac models and their applicability in high-throughput screening for drug discovery.

“Human iPSC-derived models are incredibly useful to understand cardiac pathophysiology and study compound effects. It is fantastic to see how the technology keeps evolving to offer the most accurate model to answer each question. Like the human heart, 3D models can be composed of several cell types, creating a complex in vitro environment. Compared to 2D monolayers, growing in 3D enables further development of certain cellular structures and connections that can increase the accuracy when assessing compound efficacy for cardiac diseases. This is especially useful for diseases that rely on complex cellular features, such as calcium homeostasis, or diseases in which non-myocyte cells contribute to the pathogenesis (e.g. arrhythmogenic cardiomyopathy [1]).”

iPSC-based 3D cardiac models often require millions of cells and complex culture techniques, making them expensive and less applicable for high throughput screening. Therefore, the industry generally utilizes these models in low throughput, as a confirmatory tool for late-stage screenings. Tessa strongly believes that 3D cardiac models could and should play a role in early drug discovery too and so, she has focused her PhD research on improving their applicability in this phase.

“The main goal of my project is to build an easy-to-use and reproducible, yet physiologically relevant model that accurately predicts pharmacological responses. We are generating cardiac microtissues composed of human iPSC-derived cardiomyocytes, cardiac fibroblasts, and cardiac endothelial cells [1]. These microtissues are stable, easy to culture, and only require 5000 cells, which increases their potential to be scaled up. We have also implemented a differentiation procedure for all three cell types that minimizes batch-to-batch variability during high-throughput screenings. Ultimately, automation of the full process is one of our main goals.”

As Tessa explains, 3D cardiac microtissues in 384 well-plates, with the full process automated from microtissue formation to screening, are going to be the key for pharmaceutical companies to incorporate these models early in their drug discovery pipeline. This project is being developed between the LUMC and Ncardia, which according to Tessa, is a great example of the value of academia-industry collaborations to transform innovations and knowledge into applications that can help develop better therapies.

Click here to contact our experts in cardiac diseases to discuss your questions and challenges in cardiovascular drug discovery. We will develop a solution that fits you.

Acknowledgements: This project is funded by Health Holland (MONACO-Sprint; # LSHM20063); NovoNordisk Foundation (ReNEW; #NNF21CC0073729); and a Netherlands Organization for Scientific Research (NWO)-funded VIDI fellowship (ILLUMINATE; #91715303)

References

[1] Giacomelli, E., Meraviglia, V., Campostrini, G., Cochrane, A., Cao, X., Van Helden, R. W., ... & Mummery, C. L. (2020). Human-iPSC-derived cardiac stromal cells enhance maturation in 3D cardiac microtissues and reveal non-cardiomyocyte contributions to heart disease. Cell stem cell26(6), 862-879. doi: 10.1016/j.stem.2020.05.004