Today, a doctor treating a diabetic's hard-to-heal foot ulcer
can open a sterile plastic bag, take out a swatch of artificial
skin containing two layers of living human cells, and apply it to
the wound to speed its healing.
Not far off, scientists say, are bioengineered replacements for
damaged or diseased soft tissues, cartilage, ligaments, and bone to
treat injuries and disease.
And a still more-distant prospect, but already in research, are
blood vessels and heart valves grown from scratch in the
laboratory, and a long list of other substitute body parts. Just in
the past year, scientists have isolated versatile ``stem cells''
from human embryos that can mature into any type of cell in the
body, and potentially could be used to form many kinds of tissues
and organs.
``We are on the brink of a revolution where we can create new
parts for cells, organs, tissues, and integrate them seamlessly''
into the body,'' said William Haseltine, CEO of Human Genome
Sciences in Rockville, Md. He even predicted that implanting young
cells into older people could ``dramatically extend age.''
Haseltine delivered this pep talk last month in New York City,
at what was said to be the first conference of the major players in
the fledgling commercial enterprise of tissue engineering.
A major force driving the field is medicine's shift away from a
longtime focus on infectious and other acute diseases; instead,
it's confronting a vast and aging population beset by chronic
degenerative diseases, from Alzheimer's to Parkinson's disease to
arthritis and diabetes. Indeed, these are the targets for tissue
engineering therapy.
Tissue engineering refers to rebuilding or repairing parts of
the body using a combination of artificial materials and living
cells. Often, the human cells are grown in the laboratory and then
draped onto a fibrous, biodegradable scaffolding made in the shape
of the desired tissue or organ. After implantation in the body, the
cells become part of the surrounding tissue and the nonliving
scaffolding melts away.
Who might benefit from these expected advances? Almost anyone:
patients with bone and joint injuries, cancer patients who've had
tissue removed, leaving an unsightly defect; people with
degenerative brain diseases, who might be helped by transplants of
nerve tissue; and back pain sufferers, who might have synthetic
disks placed in their backbones.
Another group might be those waiting for transplants of donor
organs; the continuing shortage of organs is said to be responsible
for 4,000 deaths each year. If tissue engineering can eventually
supply those scarce organs, it could also reduce the need for
devices like dialysis machines or artificial hearts, say advocates.
For many medical problems, ``we won't replace parts, we'll renew
them and they will be indistinguishable from one's own,'' said
Kirby S. Black, vice president for research at Cryolife, Inc., a
Kennesaw, Ga., company that is testing a tissue- engineered heart
valve.
At the New York meeting, sponsored by TechVest LLC, an
investment research firm, scientists and officials from 50
companies described bioengineered products in development or on the
drawing board.
Though in no way lacking for ideas and product prototypes, the
promised revolution is barely underway from a commercial
standpoint.
Only one bioengineered product containing living cells has been
approved by the Food and Drug Administration. It is Apligraf, an
artificial skin made by seeding human cells -- obtained from
infants' foreskins following circumcision -- onto a matrix made of
collagen, an animal protein. The cells form the two distinct layers
of actual human skin, but there are no blood vessels or hair
follicles.
Its manufacturer, Organogenesis Inc. of Canton, recently
reported that clinical trials showed that Apligraf-covered diabetic
foot ulcers healed more quickly than those treated conventionally.
Dr. Aristidis Veves of the Joslin Diabetes Center in Boston, a
researcher in the foot ulcer trials, said he believes the living
skin cells secrete growth factors that speed the ulcer repair.
Besides the slow pace of commercialization, tissue engineering
faces many technical hurdles. And it hasn't been widely embraced by
private investors, many of whom see a quicker return in Internet
ventures, for example, even though in time, ``regenerative
medicine,'' as Haseltine calls it, promises to be a huge market.
``This sector needs to get a second wind today,'' said Michael
Ehrenreich, president of TechVest. As with other innovative
technologies, he said, ``there has been unreasonable expectation at
an early stage'' which, when not quickly fulfilled, has scared off
some investors.
Michael Sefton, a professor of biomedical engineering at the
University of Toronto said the long-term goal ``is off-the-shelf
availability...of different types and sizes of organs,'' adding
that it would overcome the ethical dilemmas in allocating the
limited supply of donor organs.
Sefton heads a consortium of researchers called LIFE, which has,
as he put it, ``a very ambitious if not crazy'' goal of creating a
bioengineered heart in the next 10 years. Few in the field believe
it can be done that quickly, given that making any kind of
three-dimensional, complex organ is beyond present capabilities.
Still, researchers say growing replacement organs remains an
ultimate goal. ``I believe tissue engineering has the potential to
address the problem'' of donor organ shortages, said Robert Nerem,
who heads the joint Center for the Engineering of Living Tissues at
Georgia Institute of Technology and Emory University in Atlanta.
Among the speed bumps in tissue engineering's path, said Nerem,
are questions about obtaining cells to make products, how to mass
produce tissue-built organs, and how to get them approved by the
FDA in a reasonable time.
The prospect of using stem cells to supply the cells for tissues
and organs ``is very exciting,'' said Nerem, ``but we know so
little about how to stimulate stem cells to go down a pathway to
become a (specific) differentiated cell.''
Despite all that remains to be done, many feel that tissue
engineering will play a large role in the future of medicine. ``I
think this is the natural next frontier,'' said Michael Ehrenreich,
president of TechVest.
Among the near- and far-term applications presented at the
meeting were these:
-- CryoLife's heart valve, which is a pig's heart valve designed
to encourage the growth of a patient's own cells onto it after it
is implanted.
-- Laboratory-grown cartilage products that could replace the
meniscus in the knee joint, a cartilage often damaged by sports
injuries or arthritis. One company in cartilage research, Advanced
Tissue Sciences of La Jolla, Calif., is also testing skin
substitutes and working on tissue-engineered small blood vessels to
substitute for the leg veins commonly removed from patients to
create coronary bypass grafts.
-- Transplants of nerve cells from pigs and eye cells from humans
intended to relieve symptoms of Parkinson's disease and other brain
ailments.
-- Stem cell research aimed at creating a source of all kinds of
tissue and organ-repair cells. Researchers last year isolated
embryonic stem cells for the first time. They are obtained from
days-old human embryos, and are the cells that mature and
differentiate into all the tissues of the developing fetus.
One company, Geron Corp., of Menlo Park, Calif., hopes to
harness embryonic stem cells and make the cells that develop from
them immortal. Osiris Therapeutics, Inc., of Baltimore, is betting
on a different type of stem cell found in most organs, called
mesenchymal stem cells, that could generate a wide range of cell
types and could be obtained from adults, getting around the ethical
issues of research on embryos.
