Making a muscle: engineered fibers grow in the lab and in mice.

In a first for tissue engineering, scientists have created slivers of muscle that produce their own network of blood vessels. The accomplishment may provide insights for generating more-complex tissues, such as those that make up hearts and livers.

During the past 2 decades, scientists have had some success engineering skin, cartilage, and other thin tissues, which can recruit blood vessels from surrounding areas, or become vascularized, once in the body.

"Although this approach has been useful in many tissues, it has not been successful in thick, highly vascularized tissues, such as muscle," notes Shulamit Levenberg of the Technion-Israel Institute of Technology in Haifa. In previous experiments, the body's blood vessels didn't sufficiently infiltrate implanted pieces of engineered muscle, leaving them without enough nourishment to stay alive.

In a new approach for engineering skeletal muscle, the type of muscle that an animal can voluntarily contract, Levenberg's team combined three varieties of stem cells: those that produce skeletal muscle fibers, those that make blood vessels, and those that produce smooth muscle, which stabilizes blood vessels within muscle fibers. The researchers then spread this mixture along a spongy, biodegradable plastic scaffold and added severn proteins that encourage cell growth.

Within 3 days, Levenberg and her colleagues saw that cells had attached to the structure and were steadily growing within it. Two weeks later, the skeletal muscle stem cells had produced organized bundles of muscle fibers, with a network of blood vessels forming inside.

To see whether these blood vessels could function inside a living animal, the scientists transplanted pieces of engineered muscle into mice. They placed the tissues where muscle is normally found: under the skin, within a large muscle in the leg, and in place of an abdominal-muscle segment that had been surgically removed.

Within a month, imaging studies showed that animals' blood flowed through about 41 percent of the vessels in the implanted muscles, a result that's "pretty good for a first try," asserts Levenberg. She and her colleagues report their findings in an upcoming Nature Biotechnology.

Levenberg notes that her team's current experiments tested only whether the engineered muscle could stay alive in the receiving animal. The group is planning future studies to see whether the lab-made muscle can contract as natural tissue does.

Regardless, growing a network of blood vessels inside engineered muscle is "a major advance," says Joseph P. Vacanti, who studies tissue engineering at Harvard Medical School in Boston.

Rakesh K. Jain, also of Harvard Medical School, adds that scientists may someday use Levenberg's approach to engineer other types of tissue that need their own blood vessels. "The ability to vascularize tissue constructs would be a significant step forward in tissue engineering and regenerative medicine," he notes in a commentary that accompanies Levenberg's article.

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"The ability to vascularize tissue constructs would be a significant step forward in tissue engineering."

RAKESH K. JAIN, Harvard Medical School