Trends in cardiovascular engineering: Organizing the human heart

Abstract

The regulation of heart growth through the interaction of cell types, matrix molecules, and mechanical cues is poorly understood, yet is necessary for the heart to reach its proper size and function. Using mechanical load and vascular cell co-culture in combination with a tissue engineering approach, we have recently been able to generate organized human myocardium in vitro and to modulate cardiomyocyte alignment, proliferation, and hypertrophy within the engineered tissue construct; further, we measured contractile function and the force-length dependence of the engineered tissue as a whole. The goal of these studies has been to characterize in vitro models of human cardiac development and to work towards human therapeutics using organized, vascularized, contractile human cardiac tissue. This review will touch on the current state of knowledge in this field, give an overview of the results of our own recent findings, and present areas of active investigation and new directions for future research.

Synchronization of excitable cardiac cultures of different origin

“…[1][2][3] Cultured patches consisting of two to three layers of live cells 4,5 or even monolayers can be used to repair the cardiac conduction system. Growing cardiac tissue for regenerative medicine purposes raises some questions and among them the important one is how will the grown parts synchronize among themselves and the host tissue?…”

Modeling Human Dilated Cardiomyopathy Using Humans

“…The patient-derived iPSC-CMs were allowed to mature for 50 days, and then demonstrated a time-dependent reduction in fractional shortening similar to the age-dependent penetrance seen in human hearts. In EHTs, E848G IPSC-CMs were co-cultured with human marrow stromal cells in 3-dimensional molds 13, 14, 15. After 2 to 3 weeks, during which cells were exposed to constant external stress, E848G EHTs showed significant contractile dysfunction with a 4-fold reduction in the Starling curve slope and a >75% reduction in maximal active twitch force per area.…”

DNA methylation and chromatin dynamics during postnatal cardiomyocyte maturation

“…In addition, although blood vessels infiltrate the implanted tissues at 1 mm/day following implantation (Shimizu et al, 2006), this infiltration rate may not be sufficient for larger sized patches and is associated with some necrosis (Shimizu et al, 2006). In order to address this problem, blood vessels may be pre-formed in the tissues which link to the host vasculature and become perfused (Hirt et al, 2014;Tulloch and Murry, 2013). Electromechanical coupling also remains a major concern due to the potential induction of arrhythmias prior to coupling, however, over time the tissues do become coupled (Riegler et al, 2015).…”