"The biggest challenge has been making blood vessels that will last," says Rakesh Jain, PhD, director of the Steele Laboratory and senior author of the Nature report. "Most artificially grown vessels die quickly, but these have survived successfully for a year - which is about half a lifetime for mice." He and his colleagues also note that the introduction of genes to induce vessel growth and survival could increase the risk of cancer.
The research team began with two types of blood-vessel-related human cells - endothelial cells that form the lining of blood vessels, taken from the veins of umbilical cords, and precursors to the perivascular cells that form the supporting outer layer of blood vessels. These cells were placed into a collagen gel and grown in culture for about a day. Then the gels were implanted into cranial windows, transparent compartments placed on the brains of mice. Similar gels containing only endothelial cells were also prepared and implanted.
Within a few days both types of implants began to form long, branched tubes. Tubes in the endothelial/perivascular cell implants soon connected to the mice's own vessels and began to carry blood. They grew rapidly for about two weeks, and then reached a point of stability. However, implants containing only endothelial cells showed little or no connection to the mouse vasculature, and within two months the new vessels in those implants almost completely disappeared.
"The combined implants formed beautiful networks that survived and grew," Jain says. "As they matured, they appeared and functioned very much like normal vasculature tissue." Jain is Cook Professor of Tumor Biology at Harvard Medical School.
The researchers believe their technique could eventually allow the growth of new blood vessels from a potential recipient's own cells and could also be a model system for future studies of vessel growth and maturation.
The study's co-authors are Naoto Koike, MD, PhD; Dai Fukumura, MD, PhD; Oliver Gralla, MD, and Patrick Au, all of the Steele Laboratory; and Jeffrey Schechner, MD, of Yale School of Medicine. The research was partially supported by the National Cancer Institute.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $400 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.