Things in Dr. Anthony Atala’s lab at Wake Forest University are not always what they seem. On one lab bench, surrounded by gutted printer cartridges, lie the inner workings of an inkjet printer. But this isn’t the scene of some document-printing job gone awry. Instead, the printer has been jury-rigged to handle something much more extraordinary than ink — it now sprays tiny living cells into the three-dimensional forms of human organs.
And that’s not all. Behind ordinary-looking incubator doors lie some of the most remarkable feats of modern science — pulsing blood vessels, beating heart valves, and delicate, swollen human bladders. For nearly two decades, Atala has been perfecting the science of regenerating human tissues — essentially, the science of building new body parts. “The concept is to use the body’s own cells to make new tissues and organs for patients who need them,” he says. “We have had so many advances in various fields of science — cell biology, materials science, and stem cell biology — and all of them are coming together now to allow us to go one step further in the field of regenerative medicine, and to start to think of creating more complex organs to help patients.”
In recent years, the curative promises of embryonic stem cells and therapeutic cloning methods have outshone other research, but these techniques are still too new and unproven to yield safe and effective treatments for patients. Atala’s strategy has been to use already existing cells to create more practical solutions — for replacing everything from diseased heart muscle to worn out cartilage and failing kidney cells. “Every cell in your body is programmed to do a job, and our job is to put these cells in the right environment in the lab so they know what to do,” he says. “To us, it doesn’t matter where the cell comes from — whether it’s a bladder cell or a blood cell or an adult stem cell — we use whatever cell gets the job done.”
In most cases, that cell comes right from whatever organ is ailing, and, in the ultimate feat of personalized medicine, from the ailing organ of the patient himself. Furthest along in development are regenerated human bladders, which are already being tested in early human trials and which Atala has thoughtfully designed in small, medium and large sizes. Not far behind on the organ assembly line are heart valves and blood vessels. Atala began with the bladder not only because of his training as a pediatric urologist, but also because bladder cells are among the many that can be grown outside of the body. In fact, he says, just about every human cell can now be cultured in a Petri dish — something that wasn’t true 20 years ago, when Atala began his regeneration research. The only exceptions are pancreas, liver and nerve cells; so far these have proven too finicky to survive outside their human home.
It takes Atala about six weeks to grow a new body part. The key to his success and speed, he says, is his reliance on a patient’s own cells whenever possible. “We take a small piece of tissue from the diseased organ, grow up a bunch of normal cells, manipulate them and put them right back into the same patient,” he says. “Because we are not using cells from other people, we avoid all issues with rejection.” For the patient, that also means a shorter and more comfortable recovery, and a better chance of having the regenerated organ “take.”
Creating a working organ hinges on keeping those first few cells alive, which has proven to be the biggest challenge for Atala’s team. Each cell — whether from the bladder, skin, cartilage, or heart — prefers a different environment to grow, made up of unique cocktails of growth factors, enzymes, proteins and other nutrients. Once the incubated cells have multiplied to a sufficient number, Atala puts them through a series of rigorous tests to ensure that they look, act and function just like their normally grown siblings in the body.
And that’s when the fun starts. In order to mold human organs from a clump of cells, Atala came up with creatively constructed scaffolds that would guide the newly grown cells into shape. In most cases — for the bladder, blood vessels and valves, for example — he uses a biodegradable material made of collagen, the structural component in skin. But in order to create more complex structures, such as the heart, he needed something far more sophisticated as a matrix. That’s where the inkjet printer came in. One of Atala’s colleagues had the bright idea that if a printer can spray tiny bits of ink in a pre-set pattern, why couldn’t that same technique be used to scatter cells into pre-designed templates? So, instead of printing in one dimension, Atala’s expert re-tooled the printer to “print” its cells in successive layers; the end result is a three-dimensional mold of cells that looks suspiciously like, for example, a rudimentary heart.
Earlier this year, Atala’s group became the first to make another valuable discovery: that amniotic fluid contains stem cells. These have proven critical in helping his team to regenerate tissues from the more ornery cells of the pancreas, liver and nerves, which don’t grow as well in a lab dish. Amniotic-fluid stem cells aren’t as versatile as embryonic stem cells, which can turn into every tissue type in the body, but they can still develop into an impressive number of much-needed cell types, and Atala has already used them to grow up muscle, bone, fat and blood vessel cells, in addition to nerve and liver. He thinks that amniotic-fluid stem cells could eventually be banked, like blood cells, for universal access by any patient who might need regenerated organs. He predicts that if only about 100,000 specimens were collected from the 4 million live births each year in the U.S., it would be enough to supply 99% of Americans with appropriately matched tissues.
The first patients to receive Atala’s regenerated organs were seven young children who were transplanted with bladders grown from their own cells. Eight years after their surgery, the children are doing well, and their bladders continue to function normally. Atala now has about 20 other tissues and organs in his lab almost ready for human trials, but he refuses to rush the technology. “Our goal is to transfer these technologies from bench to bedside in the fastest way possible,” he says, “But we have gone slowly in these trials because we wanted to make sure that the tissues and organs we create are safe and effective long-term.” That kind of patience is sure to be rewarded.
