EFFICIENT DIFFERENTIATION, SCALE-UP, AND MATURATION OF IPS DERIVED CARDIOMYOCYTES

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Project Summary/Abstract Cell expansion is a critical step for cell therapy, hindered by expensive and complex bioreactor requirements to yield sufficient cell numbers for adequate dosing and requiring expensive regents to enhance functionality for increased clinical success. Similarly, in-vitro models of cardiac disease using induced pluripotent stem cell derived cardiomyocytes (iPS-CM) are of critical importance to understanding cardiac biology and disease in the human setting. However, inefficient differentiations hinder the robust translation of these models from the bench to clinically useful metrics. Similarly, iPS-CMs are inherently immature and represent fetal like phenotoypes more than their adult counterparts of more relevance for clinical utility. Thus, there is a need for the reliable production of iPS-CMs of high quality, yield, and maturity. To address this, Link provides low-shear pumpless perfusion bioreactors contatining organotypic niches for the bulk culture of cells in controllable 3D aggregates for enhanced delivery of nutrients, enhanced efficiency of directed differentiations, and increased viability and yeild due to efficient gas and nutrient exchange. These bioreactors require significantly less media than similar bioreactors and substantially less hand-on culture time than current manual workflows. Our devices are cost efficient and simple to use, democratizing patient modeling and cell therapy for both patients, researchers and providers. The increased efficiency of our developed device enables an increase in the patient pool by improving patient access, availability, and applicability to more disease subtypes.