Engineering Tissue Works Against Heart Disease

A recently published study suggests that there may be a new way to promote wound healing of tissue associated with blood vessels through tissue-engineering techniques. UC Berkeley researchers investigated two processes-haptotaxis and mechanotaxis-which are known to play a role in the remodeling of tissues.

The interaction between haptotaxis and mechanotaxis occurs during endothelial cell (EC) migration. The cells play a critical role in vascular remodeling and also determine the direction in which cells in a specific area move after injury to the area.

Haptotaxis is the observation that cells tend to migrate from a less adherent surface to a more adherent one. Mechanotaxis refers to the observation that cells tend to migrate in the direction induced by a mechanical force.

With regards to vascular tissue engineering, haptotaxis can enhance EC migration and other biological processes by controlling the distribution of extracellular matrix (ECM), which is any material part of a tissue that is not part of a cell. In this study, haptotaxis was observed in terms of EC migration from areas of low collagen density to high collagen density, since collagen is what makes up the matrix of most connective tissue.

"EC migration is also necessary for vascular assembly in engineered and native tissues, which promotes the healing of damaged tissue and the survival of tissue-engineered implants," said Steve Hsu, a UC Berkeley bioengineering graduate student and lead author of the paper. "Understanding the environmental factors that modulate EC migration is critical towards the development of improved strategies to promote vascularization in tissue-engineered constructs."

The paper appeared in the Nov. 11 issue of Biochemical and Biophysical Research Communications.

Vascular remodeling often occurs following an injury to a blood vessel, or vascular system. The cells are important in processes such as angiogenesis, embryonic vasculogenesis, and wound healing. Angiogenesis is the formation of new blood vessels from pre-existing ones, while embryonic vasculogenesis is the spontaneous formation of blood vessels during the embryonic stage.

Often times, injuries are a result of surgeries that deal with blood vessels. For example, one common surgery is the balloon angioplasty in which a usually expandable wire mesh tube is inserted into a blood vessel to unblock the blood flow within the artery.

"Therefore, rapid revascularization of the damaged site is essential in order to prevent significant vessel occlusion, a process which primarily involves EC migration from intact endothelium at the wound edges," Hsu said.

The role of endothelial cell migration is vital in humans, since the direction of migration can determine how quickly a vessel recovers after an injury.

"If we changed the direction of fluid flow or the matrix gradient, for instance, the direction of EC migration will change as well," said Hsu. "So, in that sense, EC migration can be reversible."

According to the World Heart Federation, cardiovascular disease is the world's leading cause of death in 2005. This research on cell migration may help reduce the global burden of disease through vascular remodeling.

"By understanding what environmental factors control EC migration, that will help us in the future to create novel tissue engineering strategies to treat vascular diseases to quickly regenerate a new vessel," Hsu said.

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