Effectiveness of artificial tissue depends on cell shape and type of scaffold

14 August 2012

Tissue implants made of cells grown on a sponge-like collagen scaffold have therapeutic properties that  depend on the cell shape, according to research at MIT. In addition the shape is determined by the type of scaffold on which they are grown.

The finding could allow the development of even more effective implants and also target many other diseases, including cancer.

The researchers found that cells grown on a flat surface take on a round shape in which the cells’ structural components form a ring around the perimeter of the cell. However, when cells are grown on a scaffold with surfaces of contact whose dimensions are similar in size to the cells, they mold to the curved surfaces, assuming a more elongated shape. In those cells, the structural elements — made of bundles of the protein actin — run parallel to each other.

Shape matters

For the past 20 years, researchers at MIT have been working on using endothelial cells grown on scaffolds made of collagen as implantable devices to treat blood vessel damage. Endothelial cells line the blood vessels and regulate important process such as tissue repair and inflammation by releasing molecules such as chemokines, small proteins that carry messages between cells.

Several of the devices have been tested in clinical trials to treat blood vessel damage; in the new Biomaterials study, the researchers set out to determine what makes one such tissue scaffold more effective than another. In particular, they were interested in comparing endothelial cells grown on flat surfaces and those grown on more porous, three-dimensional scaffolds. The cells grown on 3-D structures tended to be more effective at repairing damage and suppressing inflammation.

Those shapes determine what types of chemokines the cells secrete once implanted into the body. In this study, the researchers focused on a chemokine known as MCP1, which recruits inflammatory cells called monocytes.

They found that the architecture of the cytoskeleton appears to determine whether or not the cell turns on the inflammatory pathway that produces MCP1. The elongated cells grown on porous surfaces produced eight times less of this inflammatory chemokine than cells grown on a flat surface, and recruited five times fewer monocytes than cells grown on a flat surface. This helps the tissue implants to suppress inflammation in damaged blood vessels.

The researchers also identified biomarkers that correlate the cells’ shape, chemokine secretion and behaviour. One such parameter is the production of a focal adhesion protein, which helps cells to stick to surfaces. In cells grown on a flat surface, this adhesion protein, known as vinculin, accumulates around the edges of the cell. However, in cells grown on a 3-D surface, the protein is evenly distributed throughout the cell. These distribution patterns serve as molecular cues to inhibit or activate the pathway that recruits monocytes.

Precise control

The findings could help scientists manipulate their scaffolds to tailor cells to specific applications. One goal is using implanted cells to recruit other body cells that will do a particular task, such as inducing stem cells to differentiate into a certain type of cell.

“The goal is to design a material that can engineer the cells to release whatever we think is most appropriate to fight a specific disease. Then we can implant the cells and use them as an incubator,” says researcher Laura Indolfi and lead author of a paper on the research recently published online in the journal Biomaterials.