Spare Parts - growing human organs from human cells

Spare Parts - growing human organs from human cellsBioengineers foresee a time when you can grow your own organs

THE HUMAN BODY IS AN INFURIATING MIX OF fallibility and intolerance. When vital organs wear out and break down, the immune system stubbornly fights attempts to replace them. More than 60,000 Americans are waiting for transplants. Those lucky enough to receive a donor organ will still face a daunting fight for survival, forced to swallow a daily dose of immunosuppressive drugs. But in years to come patients may be able to bypass the waiting lines and overcome problems of organ rejection by getting spare body parts made from their own cells. Robert Langer of Massachusetts Institute of Technology and other bioengineers envision a time when all replaceable organs will be grown in the lab. "People used to say we were crazy," Langer says. "Our progress will depend on a more general understanding of tissues and tailoring the environment of every cell."

The process of growing an organ resembles the construction of a building. Bioengineers begin with a blueprint of the organ, and from it build a frame, or scaffold. Then comes the addition of cells--the walls, floor, and ceiling of the organ--and finally the installation of an energy source or a blood supply. So far, Langer and other leading researchers have grown skin, cartilage, a few nerves, some fingers, and bladders. Their eventual aim is to custom-tailor a complete organ using the patient's own cells as raw materials, artificial polymers as scaffolding, and enzymatic enticements to persuade the blood system to supply nourishment.

Bioengineer Linda Griffith of MIT has turned organ blueprinting into an advanced art. A human liver consists of dense tissue filled with minuscule nooks and crannies. It is composed of at least six types of cells and performs multiple functions, from storing vitamins to filtering toxins from the blood. Griffith captured some of this complexity in a three-dimensional blueprint, using computer technology developed to design airplane parts.

Once an organ exists on a computer screen, it requires a three-dimensional support structure. That's Langer's specialty. He and transplant surgeon Joseph Vacanti of Harvard Medical School forge plastic organ scaffolds that are porous and inviting to human cells. The tiny holes riddling the polymer provide homes for cells. "We can trap the cells physically inside the polymer," Langer says. "Or we can trap them chemically." As the cells grow, the polymers dissolve. The structure that remains consists almost entirely of human cells, and hence stands a better chance of evading the body's immune system.

Laura Niklason of Duke University, a former student of Langer's, has been using his cell-growing technique in pig experiments, with the ultimate goal of growing a human artery, a body part in great demand for bypass surgery Heart surgeons typically reroute blood around a clogged artery with a vein removed from the leg, but within five years, one out of three patients ends up with blocked vessels again. Niklason starts with a tubelike scaffold made of the polymer PGA and coats the inside with smooth muscle cells isolated from a pig's carotid arteries. These cells maintain the elasticity and strength of artery walls. For the next eight weeks, the crayon-size tube is bathed in a nutritive soup, rocked by gentle pulsing waves--like a fetus in a womb.

By the end of that period, the PGA scaffolding has broken down and the cells have begun secreting collagen fibers, the substance that gives healthy organs their structure. Finally; Niklason adds a layer of slippery endothelial cells, which prevents the blood from clotting, on top of the smooth muscle cells, and then puts the fabricated arteries back into the pig. In a small trial on four pigs, Niklason's arteries worked for nearly a month. Clearly; she is a long way from growing a viable human artery, but the pig experiments are a promising start.

Nephrologist David Humes of the University of Michigan has taken on an even more elaborate engineering challenge: developing a bioartificial kidney As blood courses through a kidney; it filters out urea, an ammonia-based compound that is excreted in urine. With the urea, a healthy kidney removes valuable sugars, salts, and water, substances that it then returns to the bloodstream. Dialysis separates out the same constituents but doesn't replace those that aren't toxic. So Humes constructed an external blood-filtering device--similar to a dialysis machine--but one that uses cellular parts. Humes's invention, tested only on dogs, first separates the urea and other substances from the blood, and then routes the filtrate through dozens of tubes as fine as fishing wire and lined with kidney cells. Those cells reabsorb sugars and salts and pass them back through the tubing's porous walls into the dog's blood. The cells also manufacture cytokines, proteins that signal the immune system and help avert deadly bacterial infections, which are the primary cause of death among people who experience acute kidney failure. Humes hopes for authorization from the Food and Drug Administration early this winter so he can begin testing the device on humans. And eventually he hopes to use the same biotechnology to build an implantable kidney.

Keeping an implanted organ nourished poses ye another challenge. Bioengineer Craig Halberstadt, of Carolina Medical Center in Charlotte, North Carolina, designs and grows breast tissue, which may one day replace saline implants. Developed with funding from a company called Reprogenesis, the tissue grows from cells taken from the patient's own fat. "We could take them out with liposuction--most of us have a couple of extra liters of fat," Halberstadt says.

The scaffold of the breast tissue consists of sodium alginate, a spongy, seaweed-derived substance mostly used as ice-cream thickener. To the alginate, Halberstadt attaches a peptide that will signal the vascular system that the tissue is blood-vessel friendly Then he seeds the alginate with cells, which multiply and break down the scaffold. Once implanted, the tissue will be infiltrated by blood vessels carrying nutrients. Halberstadt has successfully tested the technique only in rats but has high hopes for its success in humans.

Other organs are in the pipeline. Bladders built by bioengineer Anthony Atala have worked in dogs in his Harvard lab, where he also develops replacement kidneys and windpipes. In addition to his scaffolds, MIT's Langer has begun crafting a polymer that conducts electricity. When placed between two ends of a severed nerve, the polymer provides a trellis for nerve tissue to grow along and can carry the neuron's connective electrical impulses.

Corneas, the transparent surface of the eye, have been painstakingly constructed from layers of human cells by tissue engineers Francois Auger and Lucie Germain of Laval University in Quebec City, Canada. These may be closest to successful implantation because the engineers bypassed an artificial scaffold by cajoling the cells into producing their own collagen, which is what normal human cells do. Their strategy may allow doctors to avoid any inflammation triggered by artificial scaffolds.

Most of the bioengineers offer only cautious time lines when asked when their organ of choice will be ready The estimates of 10 or 20 years are discouraging for those waiting on transplant lists. In the meantime, the scientists are doing their best to coax Mother Nature along. "We talk to our cells," says Auger. "We are nice to them. Then they build the environment in which they are happy."


A steady supply of ARTERIES may transform heart bypass surgery.

Artificial NERVES could one day carry electrical signals between severed neurons.

A LIVER nurtured in the lab would benefit the 13,000 Americans awaiting transplants.

A bioengineered PANCREAS, lab ripened and insulin producing, may ease a diabetic's symptoms.

Fresh INTESTINES could replace tissue excised after colon cancer.

Bioengineered BLADDERS may soon provide relief from disease. Use in humans is a few years away.

A clear new CORNEA constructed with cells removed from a healthy eye could replace one clouded by disease.

Replacement SKIN already available heals leg ulcers and severe burns.

Fresh healthy BREAST tissue could fill the space left by mastectomy.

Newly grown BONES and joints may someday be built from specially cultured cells in combination with body-compatible polymers.

A lab-grown KIDNEY would clean the blood as well as protect the body from infection.

Lab-created CARTILAGE could repair damaged knees and other body parts.