Researchers at Massachusetts General Hospital have regenerated functional heart muscle in a decellularized human heart.
The donated hearts used in the study were stripped of components that would generate an immune response, and the regenerated tissue was generated from induced pluripotent stem cells, which the researchers said could come from a potential recipient.
Investigators said they developed an automated bioreactor system capable of supporting the heart during the entire recellularization process, with data from that development published last year in Circulation Research.
“Generating functional cardiac tissue involves meeting several challenges. 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,” lead author Jacques Guyette of the MGH Center for Regenerative Medicine said in prepared remarks.
The study included 73 human hearts donated through the New England Organ Bank that were determined to be unsuitable for transplantation. Researchers in the study decellularized hearts from both brain-dead donors and those who had undergone cardiac death.
The remaining cardiac scaffolds had a high retention of matrix proteins while being free of cardiac cells, study authors reported, while the regenerated hearts preserved coronary vascular and microvascular structure. The hearts were free of human leukocyte antigens that could induce rejection as well, study authors said.
The team behind the study used a new method to reprogram skin cells with messenger RNA factors to generate iPSCs from adult cells, then induced pluripotent cells to differentiate into cardiac muscle cells or cardiomyocytes.
Organs were mounted in an automated bioreactor system for 14 days that perfused the organ with nutrient solution and applied environmental stressors, such as ventricular pressure, to reproduce the conditions within a living heart. Researchers said that an analysis of the regenerated tissue found “dense regions of iPSC-derived cells” that had the appearance of immature cardiac muscle tissue and contracted functionally in response to electrical stimulation.
“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. 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,” Guyette said in a press release.
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