Significance
Compared to human stem cell-derived cardiomyocytes, neonatal rat ventricular myocytes show advanced maturation state which makes them suitable for in vitro studies of postnatal cardiac development. Still, maturation process from a neonatal to an adult cardiomyocyte has not been recapitulated in rodent cell cultures. Here, we show that low-frequency pacing and thyroid hormone supplementation of 3D engineered neonatal rat cardiac tissues synergistically yield significant increase in cell and tissue volume, robust formation of T-tubules and M-lines, improved sarcomere organization, and faster and more forceful contractions. To the best of our knowledge, 5-week old engineered cardiac tissues described in this study are the first that exhibit both ultrastructural and functional characteristics approaching or matching those of adult ventricular myocardium.
Statement of significance
Compared to human stem cell-derived cardiomyocytes, neonatal rat ventricular myocytes show advanced maturation state which makes them suitable for in vitro studies of postnatal cardiac development. Still, maturation process from a neonatal to an adult cardiomyocyte has not been recapitulated in rodent cell cultures. Here, we show that low-frequency pacing and thyroid hormone supplementation of 3D engineered neonatal rat cardiac tissues synergistically yield significant increase in cell and tissue volume, robust formation of T-tubules and M-lines, improved sarcomere organization, and faster and more forceful contractions. To the best of our knowledge, 5-week old engineered cardiac tissues described in this study are the first that exhibit both ultrastructural and functional characteristics approaching or matching those of adult ventricular myocardium.