App. Note
Organoids
iPSC

September 20, 2024

Evaluation of BioThrust's MemStir: iPSC-derived Cardiomyocyte expansion in 2L

Scalable 3D CM manufacturing for regenerative heart therapy. This proof-of-concept evaluates BioThrust’s MemStir bioreactor for expanding and differentiating iPSC-derived embryoid bodies into functional cardiomyocyte microtissues at 2 L scale.

Introduction

BioThrust is creating the innovative, bionic membrane stirrer (MemStir) for the direct expansion of (stem-) cells, cell-derived spheroids, aggregates as well as organoids in bioreactors. This application note constitutes a Proof-of-Concept (POC) preliminary study aiming at the development of a scalable production process for organoid-based heart cell therapies.

In this initial POC, Prof. Kurt Pfannkuche’s laboratory at the University of Cologne leveraged its expertise in the cultivation and differentiation of induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iPSC-CMs) into functional and transplantable aggregates. These CM-aggregates can serve as “microtissues” and potentially replace cardiac tissue loss after myocardial infarction (MI). Treatment of a MI requires approx. 8 billion CMs per dose, which means an annual global cell requirement of more than 24 quadrillion cells. This represents a significant bottleneck when using conventional 2D production systems [2–3]. In this preliminary study, a scalable process using BioThrust’s MemStir in a 2 L bioreactor setup was investigated. The project’s goal was to establish a POC for expanding and differentiating iPSC-derived embryoid bodies to functional cardiomyocytes in a 3D and 2-liter scale.

Key Takeaways

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Direct scale-up from 14 mL to 2 L (3D) in a first POC, reaching >200 million functional CMs.
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In-situ differentiation from EBs to "beating" cardiomyocytes within 7 days and a viability >90%.
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Enhanced oxygen transfer and homogeneous flow dynamics.
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No sparging and therefore anti-foam needed at any bioreactor scale or process intensity.
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Scale up to 10L and GMP process validation under way.

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