Transplanted cells regenerate muscles

A new approach for transplanting cells shows promise for regenerating injured and diseased tissues and whole organs.

Such biological engineering, which once excited the medical community, has been fraught with the difficulties of keeping transplanted cells alive and getting them to integrate with a host's body. Researchers at Harvard University's Department of Engineering and Applied Science may have solved these problems.

"We transplant the cells on a scaffold that keeps them alive, then directs them to leave in a controlled manner and migrate into the surrounding tissue," explains David Mooney, Gordon McKay Professor of Bioengineering. "This is the first time that has been done."

The strategy successfully heals lacerated muscles in mice, but the potential exists for applying it to a wide variety of situations in humans, including treatment of muscular dystrophy, heart disease, and some brain disorders, and to regenerate bone.

"We don't know yet whether the specific materials and approach we used [will] work in humans," Mooney says. "However, I think the basic concept is a very powerful one that will likely have application in humans in some form. We demonstrated the concept with muscle, and this could be useful to treat wounds and, perhaps some day, muscular dystrophy.

"In addition, it could be very useful in transplantation of cells to the heart to treat coronary artery diseases, to transplant cells that promote blood vessel formation, to transplant cells to the brain to treat various neurological conditions, and to transplant cells to promote bone generation."

Striking results

Cells can be transplanted by injecting a fluid containing them directly into the body. Typically, many of these cells die and few get incorporated into the injured tissue to help it regenerate. Mooney and his colleagues tried this with wounded mice, and, as expected, saw only a slight improvement in muscle regeneration.

Another way to transplant cells is to attach them to a scaffold that is surgically implanted. Many more cells survive, but they typically form a separate structure that doesn't integrate itself well into the surrounding tissue. Using a scaffold in some of the experimental mice did not lead to active migration out of the scaffold and into the surrounding tissue, so no improvement in regeneration occurred.

To get around these problems, Mooney's team "glued" the cells to a scaffold that contained nutrients to keep them alive longer than is usual in direct injection. The glue consisted of sticky molecules that the cells could attach to. This assisted their movement into the tissue, and drugs were added to activate the cells and coax them to leave the scaffold.

The results were striking. "Delivery of cells on scaffolds that promoted both activation and migration led to extensive repopulation of host muscle tissue and increased the regeneration of muscle fibers at the wound," Mooney notes. "If we only had one or the other signal - sticky molecules or drugs - we didn't get any significant regeneration."

Mooney started these experiments at the University of Michigan, where he got the idea of copying spaces where stem cells normally live. These consist of special niches in our bodies where the environment keeps such cells alive but prevents them from developing into more specialized cells until they move away from these homes.

"We thought we could mimic some aspects of these special living spaces in synthetic scaffolds that degrade and become absorbed by the body after the cells move away," Mooney explains. It worked.

By "we," he means Elliot Hill, a member of his Michigan team, and Tanyarut (Joy) Boontheekul, a graduate student who followed Mooney to Harvard. The three published their results in the Feb. 21 issue of Proceedings of the National Academy of Sciences.

With this success behind him, Mooney will next explore how much function the new approach can restore to damaged muscles.

He will also be collaborating with researchers at Harvard and its affiliated teaching hospitals to investigate how useful the new system will be in repairing other wounded and diseased parts of the human body.