Human-induced pluripotent stem cell-derived cardiomyocytes are widely evaluated as an alternative model for cardiac safety assessment and have the potential to improve drug discovery efficiency through early application in the drug discovery process. The constant supply of high cell numbers of high-quality cardiomyocytes generated by defined, robust, and economically viable culture processes is indispensable for the envisioned application of iPSC-derived cardiomyocytes throughout the drug discovery pipeline.
We have developed a large-scale manufacturing process for human iPSC-derived cardiomyocytes using a combination of stirred-tank bioreactor systems to assess critical process parameters at 15 mL scale, validate conditions at 100-250 mL scale, and manufacture at 1-10 L scale in an automated closed system. We established a controlled process which is robust for manufacturing of reproducible batches of high quality cardiomyocytes from a variety of iPSC lines.
The developed manufacturing process has resulted in the generation of multiple batches at purity of 87.4 ± 5.9% cTNT in >95% of the cases. The quality and functionality of the cells were confirmed using multi-electrode array and Ca2+ transient profiling. Altogether, this scientific poster shows that we can reproducibly manufacture iPSC-derived cardiomyocytes at large scale using a controlled stirred-tank bioreactor system. This hold great promise for drug discovery, providing adequate quantities of cardiomyocytes required for high throughput safety assessment at an early stage, enabling personalized safety assessment, and high-quality assays.