Navigation Links
Success of engineered tissue depends on where it's grown
Date:8/14/2012

CAMBRIDGE, Mass. -- Tissue implants made of cells grown on a sponge-like scaffold have been shown in clinical trials to help heal arteries scarred by atherosclerosis and other vascular diseases. However, it has been unclear why some implants work better than others.

MIT researchers led by Elazer Edelman, the Thomas D. and Virginia W. Cabot Professor of Health Sciences and Technology, have now shown that implanted cells' therapeutic properties depend on their shape, which is determined by the type of scaffold on which they are grown. The work could allow scientists to develop even more effective implants and also target many other diseases, including cancer.

"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 Laura Indolfi, a postdoc in Edelman's lab and lead author of a paper on the research recently published online in the journal Biomaterials.

Aaron Baker, a former postdoc in Edelman's lab and now an assistant professor at the University of Texas at Austin, is also an author of the paper.

Shape matters

For the past 20 years, Edelman has 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, Edelman and Indolfi 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.

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.

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 behavior. 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. "By designing the matrix before we seed the cells, we can engineer which factors they are going to secrete," Indolfi says.

The work should also help researchers improve on existing tissue-engineered devices and test new ones, Edelman says. "Without this kind of understanding, we can't extend successful technologies to the next generation," he says.


'/>"/>

Contact: Caroline McCall
cmccall5@mit.edu
Massachusetts Institute of Technology
Source:Eurekalert

Related biology news :

1. Drivers of marine biodiversity: Tiny, freeloading clams find the key to evolutionary success
2. 3-D tumor models improve drug discovery success rate
3. Think pink! Success of pink bacteria in oceans of the world
4. The old primates club: Even male monkeys ride their fathers coattails to success
5. First paternity study of southern right whales finds local fathers most successful
6. Successful stem cell differentiation requires DNA compaction, study finds
7. Different recipes for success in the world of plants
8. Lab-engineered kidney project reaches early milestone
9. Engineered robot interacts with live fish
10. Engineered microvessels provide a 3-D test bed for human diseases
11. New research reveals challenges in genetically engineered crop regulatory process
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/22/2016)... OTTAWA, Ontario , PROVO ... 2016 Newborn Screening Ontario (NSO), which operates ... for molecular testing, and Tute Genomics and ... process management technology respectively, today announced the launch of ... new next-generation sequencing (NGS) testing panel. ...
(Date:3/17/2016)... LONDON , March 17, 2016 ... market intelligence, forecasts the global biometrics market will ... an impressive 118% increase from 2015. Consumer electronics, ... with embedded fingerprint sensors anticipated to reach two ... Dimitrios Pavlakis , Research Analyst ...
(Date:3/14/2016)... NXTD ) ("NXT-ID" or the "Company"), ... the airing of a new series of commercials on Time ... 21 st .  The commercials will air on Bloomberg TV, ... the Street show. --> NXTD ) ("NXT-ID" or ... market, announces the airing of a new series of commercials ...
Breaking Biology News(10 mins):
(Date:4/27/2016)... ... 27, 2016 , ... The Board of Directors of Biohaven ... Tilton as Chief Commercial Officer.  Mr. Tilton joined Biohaven from Alexion Pharmaceuticals, Inc. ... responsible for the commercialization of multiple orphan drug indications. Mr. Tilton has ...
(Date:4/27/2016)... ... April 27, 2016 , ... Global Stem Cells Group CEO Benito ... the founder of GSCG affiliate Kimera Labs in Miami. , In 2004, Ross received ... cell transplantation for hematologic disorders and the suppression of graft vs. host disease (GVHD) ...
(Date:4/26/2016)... (PRWEB) , ... April 27, 2016 , ... ... of Lewis Roca Rothgerber Christie LLP as an associate in the firm’s Intellectual ... and international electrical, mechanical and electromechanical patent applications. He has an electrical engineering ...
(Date:4/26/2016)... , ... April 26, 2016 , ... Mr. Palmer created ... RPO, signing the first multi-million dollar, multi-year managed services contract in the U.S. intelligence ... Michael join our leadership team,” said John Younger, founder of Accolo. “We are ...
Breaking Biology Technology: