Recently came across this article on Tissue Engineering, and its future. Its kinda old but is really well written. It's like a story, or a fairy-tale. Even if you are not from medical/ biomedical background, it should make a very interesting and enterprising article for you. I am copy-pasting it word by word from: http://www.businessweek.com/1998/30/b3588001.htm .
This is something I am planning to work on as a career, for my PhD and lateron as well. I find it a very realistic dream, because its very well supported by a strong scientific base. Read on as you get time:
"Sean G. McCormack of Norwood, Mass., seems like your average 16-year-old boy, if a little more reckless, given his passion for mountain biking. In fact, though, he is an advance scout for a brave new world: He has the first chest grown in a lab rather than in the womb.
Sean was born without cartilage or bone under the skin on his left side, a rare congenital condition known as Poland's Syndrome. The cartilage down the center of his sternum pointed out, and his heart was virtually unprotected--you could see it beating under the skin. Doctors talked of implanting an artificial plate once he reached 21 and stopped growing. But by the time he was 12, Sean was a star pitcher for his Little League team and no longer wanted to put up with a condition that put him at risk every time he played ball. His doctor referred the family to a team of scientists and surgeons at Children's Hospital in Boston who are leading the way in growing human body parts in the lab.
Dr. Joseph Upton and Dr. Dennis P. Lund, working with tissue-engineering pioneer Dr. Joseph P. Vacanti and his brother, Dr. Charles A. Vacanti, scraped away Sean's protruding cartilage and used the cells to seed a biodegradable scaffold made of artificial polymer, molded to the shape of his torso. Dr. Yilin Cao added growth factors to the cells and ''cooked'' the concoction in a bioreactor for several weeks until a chest grew. ''The procedure was so experimental that none of the polymer companies would give us [custom-designed] material for fear of a lawsuit,'' says Joseph Vacanti. The doctors had to adapt off-the-shelf polyglycolic acid, normally used to stitch up wounds, adding to the risk of the operation.
Sean admits that ''at first I was like, 'What if they mess up?' But after a while, I put it in my head that they've done this a million times.'' Of course, they had never even done it on an animal. Nevertheless, after receiving special dispensation from the Food & Drug Administration, doctors implanted the engineered cartilage in Sean. Within a year, the boy had a normal-looking chest that was able to grow along with him. Now, four years later, the six-foot-tall teenager says: ''It's pretty cool. It looks like something I was born with.''
This is more than a nice human-interest story. It is a glimpse into the future of medicine, one in which doctors will routinely order up newly grown, living body parts whenever existing ones fail. Or they will prod the body into regenerating itself. After some 20 years of painstaking investigation into the processes by which cells grow, the nascent field of tissue engineering is ready for prime time, and dozens of startup companies are preparing commercial products. Regenerated or lab-grown bone, cartilage, blood vessels, and skin--as well as embryonic fetal nerve tissue--are all being tested in humans. Livers, pancreases, breasts, hearts, ears, and fingers are taking shape in the lab.
Scientists are even trying to develop tissues that would act as drug-delivery vessels. Salivary glands could secrete antifungal proteins to fight infections in the throat, skin could release growth hormones, and organs could be genetically engineered to correct a patient's own genetic deficiencies. ''I think [tissue engineering] holds the possibility for revolutionizing clinical medicine,'' says Kiki B. Hellman, coordinator of the FDA's biotechnology center for devices and radiological health.
The age of the biotech body is dawning. Tissue engineering offers the promise that failing organs and aging cells need no longer be tolerated--they can be rejuvenated or replaced with healthy cells and tissues grown anew. The prospect signals ''a profound revolution in medicine,'' says William A. Haseltine, a leading genetic scientist and chief executive of Human Genome Sciences Inc. in Rockville, Md. ''The current chemical era of medicine may, in retrospect, appear to be a clumsy effort to patch rather than permanently repair our broken bodies,'' says Haseltine. ''Cellular replacement may keep us young and healthy forever.''
Haseltine's genetic fountain of youth is a long way off. After all, lab-grown organs, the first step towards his vision, are still subject to the ravages of age. But tissue engineering can certainly keep failing organs from shutting down life prematurely. The principle has already been proven with the first off-the-shelf tissue approved by the FDA in May: a living skin, Apligraf, for the treatment of leg ulcers, a common ailment in the elderly. Apligraf maker Organogenesis Inc. (ORG) of Canton, Mass., turns a few cells of infant foreskin into acres of living skin that can be handled, cut to fit, and grafted on to anyone without fear of rejection or scarring. Next up: cartilage to strengthen the urethra and repair the knee and a method for replacing shinbones. Both processes are in late-stage clinical trials and are likely to be considered for FDA approval in the next year or two.
THUMBS UP.
In the next 10 years, a veritable body shop of spare parts will wend its way from labs to patients. ''It's time for us to move into humans,'' says Charles Vacanti, and he's not wasting any time. At the University of Massachusetts at Worcester, his team is growing thumb bones right now in bioreactors for two machinists who cut off their own appendages. Vacanti says one or both of the thumbs should be grafted back on to the patients this summer, with growth factors added that will encourage regeneration of the nerves and tendon. He figures that the thumbs will be operational about 12 weeks after surgery.
In Boston, meanwhile, a team of doctors at Children's Hospital led by Dr. Anthony J. Atala plans to implant a bladder grown from fetal cells into a human in the next few months. Atala's lab caused a stir in the medical community last summer when doctors there successfully used the same procedure to implant new bladders into 10 baby lambs.
Creating even the most complex organs seems possible, though still 5 to 10 years out. Researchers from around the world met in Toronto in June to set up a 10-year initiative to grow a human heart. ''It's an ambitious project but not a farfetched one,'' says Michael V. Sefton, biomaterials professor at the University of Toronto and head of the heart effort. ''The likelihood of success is very feasible.''
Other complex tissues are already taking form. At Massachusetts Institute of Technology, chemical engineer Linda Griffith-Cima is using three-dimensional printers, first developed for computer-aided design, to build up structures that are turned into mouse-size livers. And at the University of Michigan in Ann Arbor, David J. Mooney, another chemical engineer, is heading an effort to grow cosmetic breasts for women who have had theirs removed. Researchers in Sweden and California have been able to regenerate nerves in rats with severed or damaged spinal cords to the point where they can walk again--albeit weakly.
With each success, more attention is paid. After years of barely acknowledging tissue-engineering research, the National Institutes of Health plans to award 30 grants in the field, some $6 million worth, this summer. But the lack of government interest heretofore may have been a blessing in disguise. Gail Naughton, president of Advanced Tissue Sciences Inc. (ATIS) of La Jolla, Calif., says that because so little federal money was available, tissue engineers had little choice in years past but to start a company and go public in order to raise funds. ''I think that this field has moved so quickly toward reality precisely because it spent very little time in academic labs,'' she says.
Even as it gains recognition, tissue engineering remains hard to categorize. The multidisciplinary field attracts surgeons, chemical engineers, materials scientists, and genetic researchers. Products straddle the boundaries between medical devices and gene therapy. The FDA even had to set up a special task force three years ago to figure out how to regulate the products.
The FDA is playing catch-up with a technology that has been 20 years in the making. As early as 1979, Eugene Bell, professor emeritus of biology at MIT and the founder of Organogenesis, figured out how to grow skin in his lab. Since then, much of the field's progress stems from a 20-year collaboration of two fast friends--Joseph Vacanti, a pediatric surgeon at Children's Hospital, and Robert S. Langer, a chemical engineering professor at MIT. Their lab ''seeded the entire country with people doing this work,'' says Dr. Pamela Bassett, president of medical consultants BioTrend in New York.
LIFE MISSION.
The two, both 49, first met as researchers in the mid-1970s and started working on a way to grow tissue in the early 1980s. In 1986, they developed an elegantly simple concept that underlies most engineered tissue. Start with a scaffold, bent to any shape, made of an artificial, biodegradable polymer. Seed it with living cells, and bathe it in growth factors. The cells multiply, filling up the scaffold and growing into a three-dimensional tissue. Once implanted in the body, the cells are smart enough to recreate their proper tissue functions. Blood vessels attach themselves to the new tissue, the scaffold melts away, and the lab-grown tissue is eventually indistinguishable from its surroundings.
Vacanti, who is remarkably self-effacing despite his pioneering role in the field, says he is driven by his dedication to his patients. He regularly saves the lives of the smallest children by replacing their failing livers--and regularly sees others die for lack of donors. ''I recognized fairly early that the biggest problem facing me as a surgeon was the shortage of organs,'' he says. ''I've devoted my professional life to solving that problem. Wouldn't it be nice if [tissue engineering] could provide the solution?''
Nice is an understatement. A study done by Vacanti and Langer in 1993 found that more than $400 billion is spent each year in the U.S. on patients suffering from organ failure or tissue loss, accounting for almost half the national health-care bill. Some 8 million surgical procedures are performed annually to treat these disorders, yet every year 4,000 people die while waiting for an organ transplant. An additional 100,000 die without even qualifying for the waiting list.
''OVER THE BRINK.'' Those kinds of numbers represent a huge commercial opportunity as well as a humanitarian one. Dr. Peter C. Johnson, president of the Pittsburgh Tissue Engineering Initiative research consortium, estimates that the overall market for engineered and regenerated tissues could reach $80 billion. As for individual products, Michael Ehrenreich, biotech analyst with investment adviser Techvest of New York, says that the most immediately promising are those that repair damaged knee cartilage, now replaced with artificial materials. ''There are a quarter of a million meniscus [knee-joint] operations performed every year, and no good options for repair,'' says Ehrenreich. ''That's the killer app.''
Tissue engineering is dominated now by tiny startups (table, page 64), but the big drug companies are beginning to take notice. Novartis Pharmaceuticals Corp. has investments in four tissue-engineering companies, including Organogenesis. ''With the [FDA] approval of Apligraf, this whole area has really sparked the imagination of corporate executives,'' says David Epstein, vice-president of Novartis' specialty-business sector. ''We've stepped over the brink into the future of medicine.'' Novartis is not the only one with future vision. Britain's Smith & Nephew is investing some $70 million in Advanced Tissue Sciences; Amgen has a deal worth up to $465 million with Baltimore-based Guilford Pharmaceuticals to develop a compound for regenerating nerves; Stryker is funding research into bone regeneration at Creative BioMolecules of Hopkinton, Mass.; and Medtronic has agreed to invest up to $26 million in lab-grown heart valves from LifeCell in The Woodlands, Tex.
Although it may take a decade or more for some of these investments to see any returns, scientists in the field are heartened by the rapid progress of the past two to three years. ''The kinds of things that we are doing now are the kinds of things that we used to think about sitting around having beers 13 or 14 years ago,'' says Dr. Scott P. Bruder, director of bone and soft-tissue regeneration research at Baltimore-based Osiris Therapeutics Inc.
Perhaps most intriguing about tissue engineering, though, is how much the scientists don't know. Much of the excitement in biotech these days centers on figuring out complex cellular interactions and then intervening. Tissue engineering, however, is driven by surgeons and engineers who are, by nature, most interested in a successful endpoint--and less so in how they got there. ''The great thing is, we don't need to know exactly why or how cells organize into tissues,'' says Joseph Vacanti. ''We just need to know that they do.''
This all sounds easier than it actually is. Scientists must still figure out the best materials for the scaffolds that shape the organs, determine exactly the right growth factors, and pick the right cells. For bone and cartilage replacement, one possibility under investigation is a kind of premature cell called a stem cell. First isolated from human bodies in 1992, this specialized cell can turn into everything from bone to tendon to cartilage. Implanting these cells in the appropriate location can generate the full range of cells normally found at that site. While only about one in 100,000 to one in several million bone-marrow cells are stem cells, Osiris Therapeutics, partly owned by Novartis, has been able to isolate enough of them to regenerate bone in both small and large animals.
UNWELCOME STRANGERS.
Scientists also must figure out ways around the immune system's rejection of human tissue. That's not a problem for skin--it presents relatively few resistance problems since the immune system will accept some foreign dermal cells. Nor is rejection a problem when the original cells are taken from the specific patient for which they are meant. However, if off-the-shelf organs are to be transplanted, patients must take the same immunosuppressant drugs now given to them when donor organs are used.
Ideally, tissue engineers want to develop universal donor cells that would not trigger an immune response, so that body parts can be manufactured in large numbers. To that end, cells must either be genetically stripped of their rejection-provoking proteins or encapsulated in a porous membrane that the body will accept. The latter approach is nearing clinical trials for the treatment of diabetics whose pancreases are failing. BioHybrid Technologies Inc. in Shrewsbury, Mass., and Neocrin Co. of Irvine, Calif., are harvesting insulin-producing cells, called islets, from the pancreases of pigs and encasing them in a membrane that blocks the immune response while allowing the cells to do their job. The capsules are injected into the abdomen, where they go to work producing insulin.
Some companies are trying to avoid the whole immunity problem by encouraging the patient's own tissue to regenerate. Genentech Inc. (GNE), for example, announced in March that 5 of 15 patients who were given a genetically engineered protein called VEGF regrew blood vessels around the heart. Integra LifeSciences Corp. (IART) of Plainsboro, N.J., believes that just about any tissue can be regenerated by implanting a collagen matrix coated with the appropriate growth factors at the site of the damage. It already has such a matrix on the market for growing back a burn victim's skin and is in clinical trials with a similar product for the nerve endings in arms and legs. ''The body is continuously regenerating tissue,'' says Integra Chief Operating Officer George W. McKinney III. ''We're just trying to harness that process.''
Most scientists agree that regeneration is the ideal but doubt that it is always possible, or practical. ''Sometimes you have complete organ failure and can't wait for tissue to grow back,'' says Antonios G. Mikos, a bioengineering professor at Rice University. ''In truth, I think we will have both approaches. There is no one right way.''
Indeed, there are dozens of right ways in the works. Reprogenesis Inc. of Cambridge, Mass., for example, is in late-stage clinical trials with its method for using lab-grown cartilage to reinforce the urethra, a tube leading to the bladder. Weakened urethras can lead to incontinence, which afflicts an estimated 10 million people in the U.S., and reflux, a potentially fatal condition affecting about 1% of all infants in which urine backs up into the bladder. Reprogenesis removes a few cartilage cells from behind a patient's ear, grows them in the lab, and then mixes them into a gel matrix. The cells are reinserted endoscopically where the urethra meets the bladder. There, they grow to bulk up the tubal walls.
A knee-repair product called Carticel, approved by the FDA last August, uses somewhat the same principle. Made by Genzyme Tissue Repair, Carticel grows cartilage cells removed from the patient in the lab and then surgically reimplants them in the knee. No matrix is provided, however, so the cells can only be used to repair small rents. To replace the entire meniscus--that's the C-shaped pad in the knee between the thigh bone and shin bone--ReGen Biologics Inc. of Redwood City, Calif., is in clinical trials with a collagen scaffold in the shape of the meniscus. The pad is implanted in the knee to encourage regeneration of the patient's cartilage. Going a step further, Advanced Tissue Sciences is in preclinical trials with a meniscus-shaped cartilage grown in the lab that's meant to work in anyone. It hopes to start human tests by yearend.
NO MORE FILLINGS? After cartilage, look for bone products. Creative BioMolecules Inc. in Hopkinton, Mass., bases its approach on a bone-regenerating protein called OP-1. The company molds a porous scaffold out of calcium, seeds it with OP-1 and a few of the patient's own bone cells, and then reinserts the newly grown structure. Doctors reported in March that in a clinical trial of 122 patients with tibia fractures, the OP-1 graft performed as well as grafts using the patient's own bone.
The biggest market for tissue, though perhaps not the most dramatic, is the mouth. Some 10 million dental surgeries are performed each year in the U.S., on everything from teeth to periodontal ligaments, and most use artificial replacements. One of the first tissue-engineered alternatives is Atrisorb, made by Atrix Laboratories Inc. of Fort Collins, Colo. On the market since 1996, it is a bioabsorbable material loaded with growth factors and healing drugs that guides the regeneration of gum tissue.
But think of the implications if cavities could be filled with engineered tissue. Harold C. Slavkin, director of the National Institute of Dental Research at the NIH, says all the genes for making enamel have been cloned and sequenced, and lab-grown human enamel could be a reality in 5 to 10 years. Some 90 million new fillings are placed each year, and some 200 million are replaced. If those could be filled with original tissue, says Slavkin, ''we'd never have to do traditional fillings again.''
IN A HURRY.
Of course, many of these lab-produced body parts may never make it out of clinical trials. And doctors admit that they are entering uncharted waters: Who knows what might happen to an engineered organ decades after it has been implanted? Lab-grown tissues are put through far more rigorous purification processes than donor organs to make sure that they don't carry diseases, but it still is impossible to be completely sure that a replacement organ won't cause as many problems as the original a few years, or decades, down the line.
Still, there has been no evidence that these engineered tissues could turn malignant, says Joseph Vacanti. Therefore, he asks, ''can we really afford to wait for a complete understanding of how the process works?'' To him, the answer must be no. Millions of lives are hanging in the balance."
I remember a quote from Dr. APJ Abdul Kalam: "Great dreams of great dreamers are always transcended. Dream, dream and dream. Dreams convert into thoughts and thoughts convert into actions. Dreams float on an impatient wind, A wind that wants to create a new order. An order of strength and thundering of fire".
....A beautiful mind and a beautiful life!!
