SAN DIEGO and SEATTLE, May 22 /PRNewswire/ -- Bioengineering researchers
at the University of Washington will lead a multi-million-dollar effort to
grow functional human heart tissue, an undertaking that could lead to
tissue-engineered replacement hearts and set in place the technology to grow
other major organs in the laboratory.
The project, funded by a grant from the National Institutes of Health for
$10 million over five years, will initially focus on culturing thick "patches"
of cardiac muscle that could be grafted onto damaged hearts to improve their
efficiency.
The next step will be engineering a "ventricular tube," a cylinder of
rolled cardiac muscle with valves that could assist a weakened heart with
pumping. Then a full ventricle will be attempted. Eventually, researchers
hope their work will enable scientists to grow a fully functional human heart.
In growing such devices, and eventually an entire heart, researchers will
begin with a "scaffolding," or porous structure upon which cardiac cells can
gain a foothold. The scaffolding is seeded with cells then placed in a
bioreactor, which maintains a steady temperature conducive to development and
provides cells with the nutrients they need to grow and reproduce. Advanced
Tissue Sciences' (Nasdaq: ATIS) patented technology will play a key role in
the partnership's efforts.
Initially, researchers will be working with skeletal muscle cells, or
myocytes, as well as with cardiac cells. Stem cells, or cells that have the
ability to develop into specialized cells such as cardiac cells, provide
another important key. The use of stem cells on a scaffold is largely
unexplored and will be a major thrust of the project. Such cells could give
scientists a virtually never-ending supply of cardiac cells for tissue
engineering. And they may even hold clues to solving the problem of rejection
by using the patient's own cells to grow new organs.
The effort represents a public-private collaboration led by the University
of Washington. Partners, who will split the $10 million award, include
Advanced Tissue Sciences of La Jolla, Calif., the Hope Heart Institute in
Seattle, Advanced Polymer Systems of Redwood City, Calif., and the University
of Toronto. The team comprises 44 scientists working in nine UW laboratories
and five full labs at the partner companies. The project is set on a 10-year
timetable, and the group will apply to renew funding at the end of the five-
year grant.
"This is a sort of mini-Apollo mission," said principal investigator Buddy
Ratner, bioengineering professor and director of the University of Washington
Engineered Biomaterials program. "Their goal was to walk on the moon in 10
years. We also have an exciting, almost audacious goal -- to grow a human
heart ventricle.
"We have a team of people who are tops in their field who will be working
simultaneously on different aspects of the mission. The heart is a complex
organ, which makes for a complex project, so we have a complex team. We'll be
coordinating our researchers' results as we go, moving ahead as we break new
ground."
Breaking new ground will be an integral -- and exciting -- part of the
effort, according to Kip Hauch, faculty member in the UW Department of
Chemical Engineering and project coordinator.
"This field is moving so quickly, it's changing every week," Hauch said.
"We'll have to stay on the leading edge, taking advantage of advances in both
biology and engineering to address the problems that need to be solved to make
this work."
The stakes are high. In the United States alone, only 2,300 hearts are
available for transplant each year. That means 50,000 people who meet the
strict criteria for potential heart transplants die annually for want of
available organs. Many of those would be helped with a ventricular patch of
cardiac tissue, a sort of "contracting living Band-Aid" that could improve
cardiac performance to the point that a transplant wouldn't be necessary,
Ratner said. A ventricular tube could be similarly beneficial.
Designing the scaffolding is an early critical phase of the project.
Researchers will investigate the use of various polymers and techniques to
create the porous foundation, which Hauch describes as "looking like Swiss
cheese" when viewed microscopically. Preliminary findings indicate that
uniformity and pore size will be important in fostering tissue development.
Advanced Tissue Sciences will be a major resource in this area, Ratner
said. The company holds patents for seeding cells, including stem cells and
genetically engineered cells, onto scaffolds to grow three-dimensional tissue.
It uses those techniques to bioengineer commercially available replacement
skin products, as well as other tissues. The company also has patented
technology for bioreactor systems that replicate conditions inside the body to
produce engineered tissue on a large scale.
"Producing something on a small scale at the university and scaling that
up to work on an industrial scale are very different things," Ratner said.
"We'll be relying on Advanced Tissue Sciences' expertise to develop methods to
do that."
Gail K. Naughton, Ph.D., president and chief operating officer at Advanced
Tissue Sciences, said her company is looking forward to contributing its
technology, experience and intellectual property to the effort.
"We have gained valuable experience in upscaling our first commercial
products and have applied this knowledge to working with a variety of other
cell types and bioreactor systems," she said. "Working with leaders in the
field like Buddy Ratner's group at the University of Washington and the
prestigious group of researchers participating in this project, we will
continue to advance the field of tissue engineering. With our combined
efforts, the goal of tissue-engineering a human heart ventricle has the
potential to become a reality."
The team will also investigate methods of prompting cells to develop in
desired ways. For example, cells in a natural heart are lined up uniformly so
they can beat together and pump blood. It is currently possible to grow
cardiac cells in a laboratory, but they develop randomly and beat
individually. Part of the team's task involves bringing order to chaos.
An interdisciplinary UW group led by Patrick Stayton, associate professor
of bioengineering and an investigator on the project, has been able to make
cardiac cells form organized fibers by arranging natural adhesive proteins on
biodegradable scaffolds. Working with Chuck Murray, a UW cardiovascular
pathologist, and Steve Hauschka, a biochemist, the group found that cells fall
in line with the proteins, forming aligned fibers that look much like those
found in natural cardiac tissue. The line of cells beat together and show
evidence of intercalated disks, the connections between cells that provide
mechanical and electrical junctions and allow them to communicate and
coordinate with one another.
"This is the kind of preliminary research that we will be building on,"
Hauch said. "We already have promising work in doing this in two dimensions,
and we'll apply that to a three-dimensional environment."
Ratner said he knows the team faces numerous obstacles in growing living
cardiac devices. The NIH recognized that as well when it awarded the grant.
"They said they realized this is a high-risk undertaking, but the enormous
potential benefits more than justify the risk and they thought our team was
the most likely to succeed," Ratner said. "Personally, looking at the people
involved, I like our chances."
For more information, contact Ratner at (206) 685-1005, (206) 616-9718 or
ratner@uweb.engr.washington.edu, or Hauch at (206) 543-0289 or
hauch@u.washington.edu. At Advanced Tissue Sciences, contact Naughton at
(858) 713-7731.
A high-resolution magnified image of scaffolding material is available on
the Web at http://www.washington.edu/newsroom/news/images/scaffold.jpg. For B-roll
of beating, cultured cardiac cells, contact Rob Harrill at (206) 543-2580 or
rharrill@u.washington.edu. For B-roll of tissue engineering processes at
Advanced Tissue Sciences, contact Jana Stoudemire at (858) 713-7802 or
jana.stoudemire@advancedtissue.com.
Advanced Tissue Sciences Disclaimer
The discussions contained in this press release relating to research,
development, or commercialization of the Company's products that are not
strictly historical may be "forward-looking" statements which involve risks
and uncertainties. Funding provided in subsequent years over the term of the
five-year grant is contingent on the availability of funds from Congress,
subject to satisfactory performance by the Company and other collaborators,
and will be at the sole discretion of NIH. No assurances can be given that
the Company will successfully be able to obtain continued funding when needed,
develop any such products, complete clinical trials, obtain regulatory
approvals (or that any such approvals will be on a timely basis), be able to
manufacture or successfully commercialize any such products. These and other
risks are detailed in the Company's publicly available filings with the
Securities and Exchange Commission such as Advanced Tissue Sciences' Quarterly
Report on Form 10-Q for the quarter ended March 31, 2000. The Company
undertakes no obligation to release publicly the results of any revision to
these forward-looking statements to reflect events or circumstances arising
after the date hereof.
SOURCE Advanced Tissue Sciences
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CONTACT:
Jana Stoudemire of Advanced Tissue Sciences,
Inc., 858-713-7802, jana.stoudemire@advancedtissue.com; or UW
News and Information: Rob Harrill of the University of
Washington, 206-543-2580, rharrill@u.washington.edu
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