Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

MIT tissue engineers implant viable, vascularized 3D muscles

20.06.2005


Tissue derived from human embryonic stem cells



For years, a major obstacle has dashed the hopes of creating "replacement parts" for the human body: the lack of an internal, nourishing blood system in engineered tissues. Without it, thicker tissues can’t thrive, which has confined tissue engineering’s practical application to thin skin, which can recruit blood vessels from underlying tissue.

Now, researchers in Institute Professor Robert Langer’s lab at MIT have used a novel cocktail of cells to coax muscle tissue to develop its own vascular network, a process called pre-vascularization. When implanted in living mice and rats, these tissues integrated more robustly with the body’s own tissues than similar implants without blood vessels.


"What’s even more exciting than being able to make skeletal muscles for reconstructive surgery or to repair congenitally defective muscles, for instance, is that this a generic approach that can be applied towards making other complex tissues. It could allow us to do really wonderful things," says collaborator Daniel Kohane, an affiliate at MIT and assistant professor of pediatrics at Harvard Medical School.

The researchers published their work in Nature Biotechnology, available online in advance on June 19, 2005. An accompanying News and Views commentary says this "landmark paper" provides "a compelling demonstration of the benefits of pre-vascularization for engineering larger pieces of tissue."

"When I came to work with Bob Langer for my postdoc, it was my dream to vascularize a tissue," recalls first author Shulamit Levenberg, who is now on the faculty of the biomedical engineering department at Technion in Haifa, Israel where she completed these studies. She chose to tackle muscles, since they depend on blood vessels interspersed with muscle fibers and also serve as a model for highly vascularized organs such as the liver, heart, and lung.

Levenberg theorized she needed to combine three cell types: myoblasts that form muscle fibers; endothelial cells that independently self-organize into vessel tubes; and fibroblasts that are the precursors for the smooth muscle cells that stabilize the vessel amidst the tissue’s gooey extracellular matrix. "No one had tried a 3-D tri-culture scaffold before. It’s hard enough to work with one cell type, let alone three!" explains senior author Langer, who is a pioneer in tissue engineering.

In vitro experiments validated Levenberg’s hypothesis: "The endothelial cells formed vessels, recruited the fibroblasts, and differentiated them into smooth muscle cells," she says. "The differentiated fibroblasts expressed the angiogenic growth factor, VEGF, which further stimulated vessel growth." The constructs measured 5mm by 5mm by 1mm.

For implantation in living animals, the lab used immunodeficient mice and rats that would not reject the human-derived endothelial cells. At the beginning of the project, Levenberg had isolated endothelial cells from human embryonic stem cells – a first. Human derivation is key for clinical use to avoid an immune rejection.

The animal studies progressed in stages. First, the researchers implanted a muscle construct under the skin, then inserted one within a leg muscle, and finally replaced a piece of a rat’s abdominal muscle with a construct, simulating a situation applicable to trauma victims, for instance. Later tissue staining showed that the implants’ vessels grew into the host tissue and the host’s vessels grew into the constructs.

But what good are blood vessels if they don’t deliver the goods – blood? Using two non-invasive live imaging techniques (labeled lectin injected into the tail vein and a luminescent luciferase-based system), the researchers could watch the host’s blood flow into the engineered vessels. About 41% of the constructed vessels became perfused with the hosts’ blood, meaning they functioned in the living body. "That’s pretty good for a first try," Levenberg asserts.

Importantly, twice as many of the cells survived in the tri-culture implants compared to implants without endothelial cells. "The myoblasts also became even longer tubes when implanted, and they began to align themselves with the host’s muscle fibers," Levenberg recounts.

"This tri-culture system shows a whole new way of creating a vascular network in the tissue," summarizes Langer. "We’ve also demonstrated another powerful use of human embryonic stem cells."

In addition to Kohane, Levenberg and Langer collaborated with Patricia D’Amore and Diane Darland at The Schepens Eye Research Institute, Evan Garfein at Brigham and Women’s Hospital, Robert Martin of MIT’s Division of Comparative Medicine, Richard Mulligan of Children’s Hospital and Harvard Medical School, Clemens van Blitterswijk at Twente University in the Netherlands, and present and former MIT graduate students Mara Macdonald Jeroen Rouwkema.

Elizabeth Thomson | EurekAlert!
Further information:
http://www.mit.edu

More articles from Life Sciences:

nachricht Scientists enlist engineered protein to battle the MERS virus
22.05.2017 | University of Toronto

nachricht Insight into enzyme's 3-D structure could cut biofuel costs
19.05.2017 | DOE/Los Alamos National Laboratory

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

Im Focus: Hydrogen Bonds Directly Detected for the First Time

For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.

Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

Media accreditation opens for historic year at European Health Forum Gastein

16.05.2017 | Event News

 
Latest News

New approach to revolutionize the production of molecular hydrogen

22.05.2017 | Materials Sciences

Scientists enlist engineered protein to battle the MERS virus

22.05.2017 | Life Sciences

Experts explain origins of topographic relief on Earth, Mars and Titan

22.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>