Functional human hearts regenerated from skin cells

A team of researchers has used adult skin cells to regenerate functional human heart tissue, a major step forward in bioengineering organs.

A partially regenerated human heart in a bioreactor.

Bernhard Jank, MD, Ott Lab, Center for Regenerative Medicine, Massachusetts General Hospital

The day that heart transplant patients no longer need to wait for a donor match just got a little closer. Researchers from Massachusetts General Hospital have successfully grown functional heart tissue from stem cells created from skin cells. Their paper has been published in the journal Circulation Research.

The team's technique potentially allows heart tissue to be built with the patient's own cellular material, which reduces the need for an exact donor match, and also vastly lowers the chance of immunorejection.

It's not possible to simply grow an entire heart from cells. Organs require a scaffold to give the cells a shape. In the normal course of things, this scaffold, known as an extracellular matrix, is created from proteins secreted by the cells.

"Generating functional cardiac tissue involves meeting several challenges," lead author Jacques Guyette said in a statement.

"These include providing a structural scaffold that is able to support cardiac function, a supply of specialised cardiac cells, and a supportive environment in which cells can repopulate the scaffold to form mature tissue capable of handling complex cardiac functions."

Rather than grow these extracellular matrices, which would take time, the team used 73 donor hearts from the New England Organ Bank. These hearts had been determined unsuitable for transplantation.

To prepare the hearts, the team stripped them down to the extracellular matrix with a detergent solution. This removes all the living cells and leaves behind a neutral scaffold for the new cellular material.

To seed the matrices with cells, the team used a newer method that uses messenger RNA to revert the skin cells to stem cells, a more efficient technique than the older genetic manipulation. These pluripotent stem cells were then induced to grow into cardiac muscle cells.

These muscles cells were then introduced into the extracellular matrix. Within days, they grew into contracting muscle tissue. Finally, the growing heart was placed in a bioreactor with a nutrient solution, and stressors that reproduced the conditions under which a living heart operates. After 14 days, the team found dense regions of immature cardiac muscle tissue that contracted normally under 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," 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."

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