Abstract 19907: The Biomimetic Cardiac Tissue Model Differentiates Encapsulated Cardiac Progenitors by Reproducing the Hemodynamics Seen During Cardiogenesis
Introduction: Induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) provide a source of human cardiomyocytes for disease modeling and regenerative medicine. However, current iPSC-CMs are immature and lack vital structural and functional components such as ion channels, t-tubules and calcium handling mechanisms. Studies of avian and rodent heart development confirm that mechanical stimuli are critical to normal heart development and even small alterations in blood flow or hemodynamic loads results in congenital defects and impaired heart function. These studies conflict with current iPSC-CM differentiation protocols, which are accomplished in static environments in the absence of hemodynamic loading.
Hypothesis: We tested the hypothesis that differentiation of cardiac progenitors under hemodynamic loads as seen in cardiogenesis is necessary to attain functional maturation of iPSC-CMs.
Methods: In order to recreate the hemodynamic environment seen during cardiogenesis the Biomimetic Cardiac Tissue Model can precisely manipulate parameters associated with heart function like heart rate, peak-systolic pressure, end-diastolic pressure/volume, end-systolic pressure/volume, and ratio of systole/diastole, in a time dependent manner, as outlined in Fig. 1a.
Results: Differentiation of progenitors in a static environment and subjected to hemodynamic load leads to aggregation of cells as seen in Fig. 1b. However, encapsulation of progenitors soon after cardiomyocyte induction yielded cell monolayers that were able to adapt to mechanical load and showed efficient differentiation by staining of troponin (green), Fig. 2c-d, (n=3).
Conclusions: Immature iPSC-CMs generated using current differentiation protocols limit potential use of these cells for drug testing, disease modeling, and regenerative approaches. Differentiation in an environment similar to in vivo cardiogenesis may create mature iPSC-CMs and more beneficial models.
Author Disclosures: A.J. Rogers: None. V. Fast: None. P. Sethu: None.
- © 2016 by American Heart Association, Inc.