Researchers have taken another step toward creating a bioengineered human heart by using donor hearts stripped of components that would generate an immune response, and cardiac muscle cells generated from stem cells. Those specific cells, called induced pluripotent stem cells (iPSCs), could come from a potential recipient.
“Generating functional cardiac tissue involves meeting several challenges,” said lead author Jacques Guyette, of the Massachusetts General Hospital (MGH), according to Science Daily. “These include providing a structural scaffold that is able to support cardiac function, a supply of specialized cardiac cells, and a supportive environment in which cells can repopulate the scaffold to form mature tissue capable of handling complex cardiac functions.”
The study, published in Circulation Research, included 73 human hearts that had been donated through the New England Organ Bank but were deemed unsuitable for transplantation, Science Daily reported. The researchers used a process developed by team leader Harald Ott to strip the living cells from a donor organ with a detergent solution and repopulate the remaining extracellular matrix scaffold with organ-appropriate types of cells. The process had successfully been carried out on rat kidneys and lungs.
Researchers’ method led to a high retention of matrix proteins and a structure free of cardiac cells, as well as the preservation of coronary vascular and microvascular structures, Science Daily reported. Researchers also found a lack of human leukocyte antigens that could possibly lead to organ rejection. They then reprogramed skin cells with messenger RNA factors and induced the pluripotent cells to differentiate into cardiac muscle cells or cardiomyocytes while documenting patterns of gene expression to reflect developmental milestones, according to the report.
The organs were then mounted for 14 days in an automated bioreactor system developed by researchers to both perfuse the organ with nutrient solution and apply environmental stressors to reproduce conditions within a living heart, Science Daily reported.
“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 failure,” Guyette said, according to Science Daily. “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.”