A partially recellularized human whole-heart cardiac scaffold, reseeded with human cardiomyocytes derived from induced pluripotent stem cells, being cultured in a bioreactor that delivers a nutrient solution and replicates some of the environmental conditions around a living heart. (Bernhard Jank, MD, Ott Lab, Center for Regenerative Medicine, Massachusetts General Hospital)
At Massachusetts General Hospital scientists managed to regenerate functional heart muscle within donated human hearts that were first decellularized to remove the immune response triggers of the original donor. The technology was recently demonstrated with rat hearts, but the new research extended it to much larger human hearts. In this study 73 hearts, some from brain-dead donors, while others from those that died of cardiac causes, were essentially used to make scaffolds for new heart tissue. Both types of hearts did well under the decellularization process and when seeded with cells generated by reprogramming skin cells into pluripotent stem cells and then into cardiomyocytes, the resulting tissue within the organ began to spontaneously contract after a few days in the incubator.
In all about 500 million induced pluripotent stem cells were seeded into the left ventricular wall of the hearts after which they spent two weeks in a bioreactor. The in-house built device perfused the hearts and created some physical simulations to stress the heart, such as applying pressure such as that which exists within the natural organ. The tissue that was created contracted when electrically stimulated and the cardiac cells looked like immature natural ones.
“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 Jacques Guyette, PhD, lead author of the study. “Among the next steps that we are pursuing are improving methods to generate even more cardiac cells – recellularizing a whole heart would take tens of billions – 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.”
Via: Mass. General…