Fiber alignment and coculture with fibroblasts improves the differentiated phenotype of murine embryonic stem cell‐derived cardiomyocytes for cardiac tissue engineering

Abstract

Embryonic stem cells (ESCs) are an important source of cardiomyocytes for regenerating injured myocardium. The successful use of ESC-derived cardiomyocytes in cardiac tissue engineering requires an understanding of the important scaffold properties and culture conditions to promote cell attachment, differentiation, organization, and contractile function. The goal of this work was to investigate how scaffold architecture and coculture with fibroblasts influences the differentiated phenotype of murine ESC-derived cardiomyocytes (mESCDCs). Electrospinning was used to process an elastomeric biodegradable polyurethane (PU) into aligned or unaligned fibrous scaffolds. Bioreactor produced mESCDCs were seeded onto the PU scaffolds either on their own or after pre-seeding the scaffolds with mouse embryonic fibroblasts (MEFs). Viable mESCDCs attached to the PU scaffolds and were functionally contractile in all conditions tested. Importantly, the aligned scaffolds led to the anisotropic organization of rod-shaped cells, improved sarcomere organization, and increased mESCDC aspect ratio (length-to-diameter ratio) when compared to cells on the unaligned scaffolds. In addition, pre-seeding the scaffolds with MEFs improved mESCDC sarcomere formation compared to mESCDCs cultured alone. These results suggest that both fiber alignment and pre-treatment of scaffolds with fibroblasts improve the differentiation of mESCDCs and are important parameters for developing engineered myocardial tissue constructs using ESC-derived cardiac cells.

Cardiomyocyte behavior on biodegradable polyurethane/gold nanocomposite scaffolds under electrical stimulation

“…Although many PU-based materials have been developed for providing vascular grafts, only few PU scaffolds have so far been studied in the context of myocardial tissue engineering [39,40], even though PU is easy to implant into muscle tissue, because it is stiffer than typical hydrogels. An important goal for myocardial tissue engineering must be the fabrication of materials that allow for the synchronization of electrical signals, and thus enhance the contraction of cardiomyocytes in the scaffold material so that a homogeneous total contraction of the engineered patch is guaranteed.…”

Plasma-functionalized electrospun matrix for biograft development and cardiac function stabilization

“…In vitro evaluations underpinned the suitability of electrospun membranes for cardiomyocyte guidance and differentiation as well as maintenance of their contractile function [20][21][22]. The fibrous, anisotropic architecture of electrospun scaffolds compared to solid substrates proved superior for cardiomyocyte maturation and, in particular, cell infiltration and multi-layered tissue formation [23][24][25].…”

Xylan polysaccharides fabricated into nanofibrous substrate for myocardial infarction

“…Lee et al (2008) observed the cardiac fibroblasts promote remodeling of a preformed collagen matrix and aid in the formation of compact cardiac-like tissue [30]. Parrag et al (2011) studied murine embryonic stem cells derived cardiomyocytes (mESCDCs) attached on polyurethane (PU) scaffolds and also showing construct contraction [31]. These PU scaffolds are important for developing engineered myocardial constructs using mESCDCs and also consider human ESCDCs induced pluripotent stem cell-derived cardiomyocytes for clinically relevant cardiac repair.…”