Success of engineered tissue depends on where it's grown
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.
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.
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.
Provided by Massachusetts Institute of Technology
- Scientists discover cancer-fighting role for cells Jan 19, 2011 | not rated yet | 0
- Tissue engineered scaffolding allows reproduction of cartilage tissue May 09, 2007 | not rated yet | 0
- Researchers find novel way to repair airway injuries May 06, 2008 | not rated yet | 0
- Personal stem cell banks could be staple of future health care Nov 01, 2011 | not rated yet | 0
- Human embryonic stem cell -- derived bone tissue closes massive skull injury Dec 02, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
Medical research 12 hours ago | 5 / 5 (3) | 0 |
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
Medical research May 17, 2013 | 4 / 5 (4) | 0 |
Scientists investigating the interaction of a group of proteins in the brain responsible for protecting nerve cells from damage have identified a new target that could increase cell survival.
Medical research May 17, 2013 | 5 / 5 (1) | 0
New findings by researchers carrying out experiments at the U.S. Department of Energy Office of Science's Advanced Photon Source (APS) help explain why some drugs that interact with two kinds of human serotonin ...
Medical research May 17, 2013 | 4 / 5 (1) | 0 |
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
12 hours ago | 4.8 / 5 (4) | 0 |
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
11 hours ago | 5 / 5 (1) | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
12 hours ago | 5 / 5 (2) | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
16 hours ago | not rated yet | 0
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
11 hours ago | 5 / 5 (1) | 0
The devastating effect of Alzheimer's disease on bilingual people has been thrown into focus in Canada, where the sudden loss of a second language can leave sufferers feeling like strangers in their own country.
14 hours ago | not rated yet | 0