BioTechniques
04/04/2016 Amber Dance, PhD
Right now, the only cure for heart failure is a new ticker from a deceased organ donor. But scientists are getting closer to fashioning a lab-made replacement from cadaver organs plus live cells.
The ghosts of people who die might someday live on in heart transplant patients. Not their spirits—but their hearts, flushed of cells to make what some scientists call a “ghost organ” that is then repopulated with cells matched to the transplant recipient. Researchers from Massachusetts General Hospital in Boston now report in the journal Circulation Research that they have scaled up the process of decellularization and repopulation, approaching what is needed to engineer a full-size human heart.
The national heart transplant supply of about 2500 per year does not meet the demand by the nation’s 4000 transplant-ready heart failure patients, many of whom languish on the waitlist. Harald Ott hopes to build replacements based on the 5000 donor hearts per year that are deemed unsuitable for a transplant—for example, because of poor function—but conveniently provide the structure of a human heart.
In Ott’s lab, Jacques Guyette and colleagues acquired 73 “nontransplantable” hearts from the New England Organ Bank. They flushed them with a series of detergents, water, and buffer to dissolve the cells and then treated the hearts with endonuclease to eliminate lingering DNA.
During the process, the hearts went from muscular and red to flabby and white. What remained was the extracellular matrix—collagen, proteoglycans, and the like—but none of the pesky antigens that trigger organ rejection.
To repopulate the ghostly scaffold, the authors differentiated iPS cells into cardiomyocytes. They cultured these on a small patch of the decellularized matrix and then on a single muscle fiber. In both cases, the cells survived for more than 2 months and even began to beat.
For the big test, the authors seeded a portion of whole ghost hearts. They placed these in a custom-built chamber, complete with circulating media and a pressure system to provide the mechanical stress needed for cardiomyocyte maturation. They injected 500 million cardiomyocytes into a 5-centimeter-square spot in the left ventricle. After 2 weeks, the authors gave the cells an electric shock, and the muscle contracted.
When the authors dissected their repopulated hearts, they saw that the cells had filled about half of the target area. “The ultimate goal of creating a whole bioartificial heart is several years away,” Guyette said. Scientists will have to recellularize the whole thing—which would require billions of cardiomyocytes—and optimize the culture conditions. In the shorter term, the scientists hope to create grafts that could assist a patient’s ailing heart.
Reference
Guyette JP, Charest JM, Mills RW, Jank BJ, Moser PT, Gilpin SE, Gershlak JR, Okamoto T, Gonzalez G, Milan DJ, Gaudette GR, Ott HC. Bioengineering human myocardium on native extracellular matrix. Circ Res. 2016 Jan 8;118(1):56-72.
04/04/2016 Amber Dance, PhD
Right now, the only cure for heart failure is a new ticker from a deceased organ donor. But scientists are getting closer to fashioning a lab-made replacement from cadaver organs plus live cells.
The ghosts of people who die might someday live on in heart transplant patients. Not their spirits—but their hearts, flushed of cells to make what some scientists call a “ghost organ” that is then repopulated with cells matched to the transplant recipient. Researchers from Massachusetts General Hospital in Boston now report in the journal Circulation Research that they have scaled up the process of decellularization and repopulation, approaching what is needed to engineer a full-size human heart.
The national heart transplant supply of about 2500 per year does not meet the demand by the nation’s 4000 transplant-ready heart failure patients, many of whom languish on the waitlist. Harald Ott hopes to build replacements based on the 5000 donor hearts per year that are deemed unsuitable for a transplant—for example, because of poor function—but conveniently provide the structure of a human heart.
In Ott’s lab, Jacques Guyette and colleagues acquired 73 “nontransplantable” hearts from the New England Organ Bank. They flushed them with a series of detergents, water, and buffer to dissolve the cells and then treated the hearts with endonuclease to eliminate lingering DNA.
During the process, the hearts went from muscular and red to flabby and white. What remained was the extracellular matrix—collagen, proteoglycans, and the like—but none of the pesky antigens that trigger organ rejection.
To repopulate the ghostly scaffold, the authors differentiated iPS cells into cardiomyocytes. They cultured these on a small patch of the decellularized matrix and then on a single muscle fiber. In both cases, the cells survived for more than 2 months and even began to beat.
For the big test, the authors seeded a portion of whole ghost hearts. They placed these in a custom-built chamber, complete with circulating media and a pressure system to provide the mechanical stress needed for cardiomyocyte maturation. They injected 500 million cardiomyocytes into a 5-centimeter-square spot in the left ventricle. After 2 weeks, the authors gave the cells an electric shock, and the muscle contracted.
When the authors dissected their repopulated hearts, they saw that the cells had filled about half of the target area. “The ultimate goal of creating a whole bioartificial heart is several years away,” Guyette said. Scientists will have to recellularize the whole thing—which would require billions of cardiomyocytes—and optimize the culture conditions. In the shorter term, the scientists hope to create grafts that could assist a patient’s ailing heart.
Reference
Guyette JP, Charest JM, Mills RW, Jank BJ, Moser PT, Gilpin SE, Gershlak JR, Okamoto T, Gonzalez G, Milan DJ, Gaudette GR, Ott HC. Bioengineering human myocardium on native extracellular matrix. Circ Res. 2016 Jan 8;118(1):56-72.