Cell combo yields blood vessels

By Eric Smalley, Technology Research News

One of the main challenges to growing replacement organs is finding ways to get blood vessels to form inside the tissue before it is placed inside the body.

Researchers have been remarkably successful in recent years at growing different types of tissue, but getting relatively large pieces of engineered tissue to survive in the body requires coaxing networks of tiny blood vessels to form as the tissue grows in the laboratory.

Researchers from the Massachusetts Institute of Technology, Twente University in The Netherlands, Brigham and Women’s Hospital, Massachusetts General Hospital, the Boston Children’s Hospital, the Schepens Eye Research Institute, and Harvard Medical School have brought tissue engineering a significant step forward with a method for growing muscle tissue that contains blood vessels. They also showed that tissue grown using the method survives better in mice and rats than tissue formed using previous techniques.

The technique paves the way to growing viable, vascularized tissue from cells. "In vitro vascularization can improve vascularization in vivo and survival of the implant," said Shulamit Levenberg, a former research associate at the Massachusetts Institute of Technology and now a senior lecturer at Technion-Israel Institute of Technology in Israel.

This is needed to realize the long-held dream of growing replacement parts like muscles and internal organs.

The key to the breakthrough was seeding several types of cells on a three-dimensional scaffold to form skeletal muscle tissue, said Levenberg.

Tissue engineering involves seeding a scaffold with thousands of cells that are precursors to the specialized cells of particular types of tissue. The scaffolds are sponge-like polymer materials that degrade over time as the tissue forms.

Efforts aimed at growing muscle tissue usually begin with myoblast cells, which fuse together to form skeletal muscle fibers. Skeletal muscle fibers arranged in parallel and linked by connective tissue form skeletal muscle tissue, which attaches to the skeleton and moves the body.

The researchers added two other types of cells to the process -- endothelial and fibroblast -- with the aim of promoting blood vessel growth as the tissue forms. Endothelial cells form the inner lining of blood vessels throughout the circulatory system. Fibroblasts are the precursors to connective tissue cells. The endothelial cells and fibroblasts were derived from human embryonic stem cells.

When the researchers combined myoblasts and endothelial cells in the scaffold, they found that the endothelial cells organized themselves into blood vessels within the growing tissue. When the researchers used all three types of cells, the fibroblasts formed smooth muscles cells around about 65 percent of the blood vessels, which stabilized the vessels.

The researchers implanted tissue grown for two weeks in the laboratory under the skin of mice, within the quadriceps muscle of rats, and as a replacement of a segment of abdominal muscle in mice. The precursor cells continued to form muscle, blood vessel and connective tissue cells in all three types of implants, according to the Levenberg.

Two weeks after implantation many of the engineered blood vessels had connected to the host animal's native blood vessels, and about 40 percent carried blood from the host, according to Levenberg.

Implanted tissue grown with the researchers' technique yielded about 30 functional blood vessels per square millimeter compared to about 20 in tissue grown from muscles cells only, according to Levenberg. The blood vessels in the researchers' tissue were also larger, she said.

The research shows that forming blood vessels in engineered tissue improves the vascularization and survival of tissue implants, and that using multiple types of seed cells is important for forming the blood vessels in the tissue, said Levenberg.

The researchers' next steps are to apply the technique to other types of tissue and to use the method to produce vascularized tissue implants that function rather than simply survive inside the body.

Levenberg's research colleagues were Jeroen Rouwkema and Clemens A. van Blitterswijk of Twente University in The Netherlands, Mara Macdonald, Robert Marini and Robert Langer of the Massachusetts Institute of Technology, Evan S. Garfein of Brigham and Women's Hospital, Daniel S. Kohane of Massachusetts General Hospital, Diane C. Darland and Patricia A. D'Amore of the Schepens Eye Research Institute and Harvard Medical School, and Richard C. Mulligan of Children's Hospital in Boston and Harvard Medical School.

The work appeared in the June 19, 2005 issue of Nature Biotechnology. The research was funded by the National Institutes of Health (NIH).

Timeline:  Unknown
Funding:  Government
TRN Categories:  Biotechnology
Story Type:   News
Related Elements:  Technical paper, "Engineering Vascularized Skeletal Muscle Tissue," Nature Biotechnology, June 19, 2005


June 29/July 6, 2005

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