Scientists may have made a breakthrough in bioengineering human hearts.
They've used donor hearts stripped of components that would generate an immune response and have re-populated them with pluripotent stem cells (iPSCs) which could come from a potential recipient.
"Generating functional cardiac tissue involves meeting several challenges," said Jacques Guyette, lead author of the new report. "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."
In 2008, the researchers developed a procedure for stripping the living cells from a donor organ with a detergent solution. Then, they found a way to repopulate the remaining extracellular scaffold with organ-appropriate types of cells. Now, the scientists have analyzed the matrix scaffold remaining after doing the same process to whole human hearts.
In this latest study, the researchers examined a total of 73 human hearts that couldn't be used for transplantation. The researchers then decellularized the hearts and examined the remaining cardiac scaffolds. After that, they then reprogrammed skin cells with messenger RNA factors. Then, they caused the pluripotent cells to differentiate into cardiac muscle cells. In the end, the researchers managed, for the first time, to regenerate human heart muscle from pluripotent stem cells within a cell-free, human, whole heart matrix.
"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," Guyette said. "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."
The findings could be huge for creating hearts that are specially designed for a patient.
"Generating personalized functional myocardium from patient-derived cells is an important step towards novel device-engineering strategies and will potentially enable patient-specific disease modeling and therapeutic discovery," Harald Ott, team leader of the new study, said. "Our team is excited to further develop both of these strategies in future projects."
The findings are published in the journal Circulation Research.
