PROJECT SUMMARY/ABSTRACT
This project is to develop strategies to promote maturation of engineered cardiac microtissues containing
cardiomyocytes derived form induced pluripotent stem cells to serve as a novel in vitro cardiac tissue model.
Traditional 2D cardiac cell culture model systems have many limitations, such as the inability to fully reproduce
the cellular microenvironment in vivo, changes in cell morphology, phenotypes, and bioactivities
in comparison with their in vivo counterparts. Engineered human cardiac microtissues (cMTs) made of cardiac
cells derived from human induced pluripotent stem cells (hiPSCs) have great potentials to become an ideal 3D
cardiac tissue model. However, the fetal-like state of hiPSCs derived cardiomyocytes (hiPSC-CMs) have results
in compromised functionality of these engineered cMTs. Many approaches have been used to mature hiPSC-
CMs. But maturation of hiPSC-CMs has not yet been fully achieved. Here, we hypothesize that interactions
between vascularized cardiac extracellular matrix (ECM) and hiPSC-CMs are critical to promote phenotypic and
functional maturation of the engineered human cMTs. Our hypothesis will be tested by accomplishing three
specific aims: (1) Assess the effects of vascularized cardiac ECM on maturation of hiPSC-CMs; (2) Engineer
human cardiac microtissues composed of vascularized cardiac ECM and hiPSC derived cardiac cells; and (3)
Determine the roles of mechanical stimulation in improving maturity of engineered human cMTs. Our findings
will generate new scientific knowledge on the roles that cardiac ECM and vasculature play in maturation of
cardiomyocytes and cardiac tissue. The developed methods and platforms will facilitate the discovery of new
developmental drivers to cell and tissue maturation. This project will be an important step towards the
development of 3D cardiac constructs with structural, physiological, and functional properties resembling human
native cardiac tissue, which are crucial for new drug development and studying pathological mechanisms.
Furthermore, this project will greatly enhance research infrastructure at the University of Akron and provide
opportunities for underrepresented students to be professionally trained and gain extensive research
experiences in stem cells, natural biomaterials and cardiac tissue engineering.