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 Seeing on the Quick: New Insights into Active Vision in the Brain
15.08.2018 | Eberhard Karls Universität Tübingen

nachricht New Approach to Treating Chronic Itch
15.08.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

Unraveling the nature of 'whistlers' from space in the lab

15.08.2018 | Physics and Astronomy

Diving robots find Antarctic winter seas exhale surprising amounts of carbon dioxide

15.08.2018 | Earth Sciences

Early opaque universe linked to galaxy scarcity

15.08.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>