Functional Cardiac Muscle Cells can be Successfully Regenerated

BIOENGINEERED human hearts are becoming a reality after a team of researchers successfully generated cardiomyocytes (cardiac muscle cells) with the help of recellularisation support systems.

“Regenerating a whole heart is most certainly a long-term goal that is several years away, so we are currently working on engineering a functional myocardial patch that could replace cardiac tissue damaged due to a heart attack or heart failure,” stated Dr Jacques Guyette, Massachusetts General Hospital; Harvard Medical School, Boston, Massachusetts, USA.

Seventy-three donated human hearts deemed unsuitable for transplantation were decellularised in the study, which used a method initially developed in rat hearts. As well as extending the method to human cell generation, the new study also characterised the matrix at various stages of the process. Following decellularisation, the remaining cardiac matrix scaffolds were found to preserve a high frequency of matrix proteins and coronary vascular and microvascular structures, along with a lack of human leukocyte antigens that could cause rejection of the generated cells.

Following decellularisation, induced pluripotent stem cells (iPSCs) were generated using messenger RNA factors that re-programme skin cells, inducing the cells to differentiate into cardiomyocytes. Throughout this process the patterns of gene expression were documented, providing insight into the developmental pathways of these cells. Approximately 500 million iPSC-derived cardiomyocytes were then reseeded into the decellularised matrix tissue of the left ventricular wall. The hearts were mounted for 14 days using an automated bioreactor system that provided nutrients and ventricular pressure in order to mimic living heart conditions. The derived cells began spontaneously contracting after several days in culture, and exhibited functional contraction in response to electrical stimulation.

This research has provided a new platform for innovative bioengineering in cardiology. Speaking on the future direction of research, Dr Harald Ott, Assistant Professor of Surgery, Massachusetts General Hospital; Harvard Medical School added: “Generating personalised functional myocardium from patient-derived cells is an important step towards novel device-engineering strategies and will potentially enable patient-specific disease modelling and therapeutic discovery. Our team is excited to further develop both of these strategies in future projects.”

Kerys Martin