A multinational team of researchers has grown new muscle complete with its own network of blood vessels in the laboratory, and implanted the new muscle in a living mouse. The accomplishment is a first for tissue engineering, according to a report in the June 19 issue of Nature Biotechnology.
Lead researcher Dr. Shulamit Levenberg of the Technion-Israel Institute of Technology, along with scientists from the Massachusetts Institute of Technology, grew the muscle from scratch by seeding a sponge-like, three-dimensional plastic scaffold with myoblasts and endothelial cells, which are the precursors to mature skeletal muscle and blood vessel cells. The researchers also added connective tissue cells called fibroblasts to the mix as a crucial third ingredient.
"The idea is that this hopefully will be used to repair or replace damaged muscle tissue when needed," Levenberg says.
In the near future, Levenberg explains, a simple muscle biopsy might provide the "seed" cells for a person’s own engineered replacement muscle. For example, the lab-grown muscles could replace tissue lost to severe trauma such as burns, or build up muscle that has weakened or wasted away in diseases like AIDS.
Until now, most scientists have not attempted to provide engineered tissue with its own blood supply. Instead, they have implanted the new tissue into the body and waited for the body itself to infiltrate the tissue with blood vessels.
"Although this approach has been useful in many tissues, it has not been as successful in thick, highly vascularized tissues such as the muscle," Levenberg says.
To create muscle tissue that would be threaded through with blood vessels before being implanted, the researchers mixed different cell types together on the plastic mold for the tissue. The different cells quickly organized themselves on the scaffold, with the myoblast cells transforming into aligned and elongated muscle fiber tubes and the endothelial cells organizing themselves in tubes nestled between the myoblasts.
By adding fibroblast cells to the scaffold, the researchers were able to significantly boost the growth of the blood vessel network forming within the muscle tissue. Thanks in part to the stabilizing influence of the fibroblasts, the surface area covered by vessel cells and the percentage of vessel-like structures in the tissue doubled within two weeks.
The endothelial cells and the vessel networks that they provide may also be useful in coaxing the muscle cells to differentiate and organize themselves in a mature, three-dimensional tissue, the researchers suggest.
To test the new muscles’ therapeutic potential, the researchers implanted them within three groups of living mice. The new muscle was placed under the skin of the back and within a thigh muscle, and used to completely replace an abdominal muscle segment. The transplanted muscle continued to grow and develop within the mice’s bodies.
Endowing the muscle tissue with its own blood supply boosted the new tissue’s chance of survival and of connecting seamlessly with the mice’s own blood vessel networks, they concluded.
The study was supported by the United States’ National Institutes of Health.
The Technion-Israel Institute of Technology is Israel's leading science and technology university. Home to the country’s only winners of the Nobel Prize in science, it commands a worldwide reputation for its pioneering work in nanotechnology, computer science, biotechnology, water-resource management, materials engineering, aerospace and medicine. The majority of the founders and managers of Israel's high-tech companies are alumni. Based in New York City, the American Technion Society is the leading American organization supporting higher education in Israel, with 17 offices around the country.