Myocardial infarction and cardiac insufficiencies are a leading cause of pre-mature death worldwide. Induced pluripotent stem cells (iPSCs) offer a potent cell source for the de novo generation of human cardiomyocytes, which might serve to replace lost heart muscle. Applications of such cell products are considered innovative but complex, multi-layered therapeutic concepts.

Addressing the elaborate requirements, we have formed a multidisciplinary team of experts in stem cell biology and bioprocessing, veterinarians and clinician scientists experienced in preclinical large animal models, imaging and clinical translation of innovative therapies. This team is complemented by pathologists and toxicologists, experts in ethical and legal aspects of life sciences, and by industrial partners with experience in the production of GMP-compliant cell culture components and biological implants.

Our consortium has cooperated successfully towards developing GMP-compliant reprogramming and scalable expansion and differentiation of highly enriched cardiomyocyte preparations in stirred mass bioreactors using defined culture media. Moreover, clinical and commercial translation of hiPSC-based heart repair strategies are spearheaded applying the most relevant pre-clinical model, i.e. non-human primates, to assess hiPSC-cardiomyocyte function and safety. Importantly, the planned project aims at answering the question, whether the injection of small iPSC-derived muscle aggregates is safe and can lead to substantial recovery of heart function without elimination of existing scar tissue.

The presentation will address the development of protocols for GMP compliant reprogramming and production of iPSCs and highly enriched cardiomyocytes under scalable culture conditions, as well as their application in a nonhuman primate model of myocardial infarction.