Producing High Quality CRISPR-Cas9 Edited hiPSCs for Cardiac Disease Modeling

The Nobel prize winning discovery of human induced pluripotent stem cells (hiPSCs) facilitated a new era of disease modeling in vitro. This event inspired clinicians and scientists alike to use those cells for regenerative medicine, or for modeling of genetic diseases, to gain further insights into disease mechanisms on a cellular level. However, experimental studies using hiPSCs can experience high inter- and intra-experimental variability further fueling the reproducibility crisis in life sciences.

In the past 10 years much progress has been made in defining quality criteria (QC) for hiPSCs to achieve genome stability and high pluripotency over prolonged culture duration. These QC parameters include single cell clonal selection, karyotyping, pluripotency assessment and the establishment of master cell banks, especially in the context of CRISPR-Cas9 genome edited hiPSCs. Additionally, Numerous cardiac differentiation protocols have been established using monolayer (ML) adherent or 3D suspension cultures. However, generating large numbers of high quality human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with high consistency between batches, different cell lines and cryo-storage has remained challenging leading to poor reproducibility of experimental results.

The featured speakers used a stirred suspension bioreactor system to create an optimal environment for cell growth and differentiation. This enabled them to create a unified differentiation protocol that can be applied to a variety of hiPSCs (patient and control lines) with high cardiomyocyte content and reduced batch-to-batch variability. Using a wide array of cardiac disease modeling assays, they then confirmed high reproducibility of cryo-preserved hiPSC-derived cardiomyocytes.

Join this webinar to learn about optimizing the growth and differentiation of human induced pluripotent stem cells (hiPSCs) into cardiomyocytes and enhancing cardiac disease modeling.

Speaker

Maksymilian Prondzynski, PhD, Instructor, The Department of Cardiology, Boston Children's Hospital and Harvard Medical School

Maksymilian Prondzynski currently works as an Instructor in the Department of Cardiology at Boston Children’s Hospital focused on the study of pediatric cardiomyopathies. He received his PhD from the University of Hamburg (Germany) investigating underlying cellular and gene regulatory mechanisms leading to the development of inherited cardiomyopathies using patient-specific or CRISPR/Cas9-edited human iPSC-derived cardiomyocytes (hiPSC-CMs). His efforts are aimed at improving patient outcomes by finding unique entry points for prevention, early detection and reversal of cardiac dysfunction in vitro.

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