Bioengineered Human Myocardium Successfully Regenerated

A new study shows that native cardiac extracellular matrix (ECM) scaffolds could support the seeding of human stem cell-derived cardiomyocytes in order to create functional myocardial-like tissue of multiple complexities.

Researchers at Massachusetts General Hospital (MGH; Boston, MA, USA) and the Harvard Stem Cell Institute (HSCI; Cambridge, MA, USA; hsci.harvard.edu) conducted a study involving 73 donated human hearts that were determined to be unsuitable for transplantation. The first step involved decellularization of the hearts. A detailed characterization of the remaining cardiac scaffolds confirmed a high retention of matrix proteins, the preservation of coronary vascular and microvascular structures, and freedom from human leukocyte antigens that could induce rejection.

The ECM scaffolds were then reseeded with human cardiomyocytes derived from induced pluripotent stem cells (iPSCs), and cultured in a bioreactor that delivered a nutrient solution and replicated some of the environmental conditions that envelope a living heart. The researchers succeeded in maintaining the cardiac tissue constructs in culture for 120 days, demonstrating definitive sarcomeric structure, cell and matrix deformation, contractile force, and electrical conduction.

To show that functional myocardial tissue of human scale could be built using the platform, they then partially recellularized human whole-heart scaffolds with human induced iPSC-derived cardiomyocytes. Under the biomimetic culture, the seeded constructs developed force-generating human myocardial tissue and showed electrical conductivity, left ventricular pressure (LVP) development, and metabolic function. The study describing the process was published in the January 2016 issue of Circulation.

“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 a heart attack or heart failure,” said lead author Jacques Guyette, PhD, of the MGH Center for Regenerative Medicine (CRM). “Among the next steps that we are pursuing are improving methods to generate even more cardiac cells, optimizing bioreactor-based culture techniques to improve the maturation and function of engineered cardiac tissue, and electronically integrating regenerated tissue to function within the recipient’s heart.”

Related Links:
Massachusetts General Hospital
Harvard Stem Cell Institute