Playing God can take decades.
In 2006, Dr. Anthony Atala of the Wake Forest School of Medicine published a breakthrough study. In the seven years before, he had successfully grown and replaced diseased bladders in seven children. Grew them, as in he took portions of the patients’ original bladders, coaxed the cells into a regenerative state, and then molded them on a biodegradable scaffold into the shape of a bladder. The bladders were then transplanted into the children, and after years of observations, he called the entire operation a success.
So are lab-grown bladders now a common treatment for end-stage bladder disease?
No. That 2006 report was just the end of phase one of the four-phase clinical trial process. Each phase of clinical trials increases the size of the subject pools, testing safety and long-term outcomes. For pharmaceuticals, the process can take 15 years. For something more invasive such as a transplant procedure, it’s bound to take longer, decades even.
“We didn’t got to phase two until several years after that,” Atala says of the initial publication. “And many people have asked us, ‘Well, why did you wait so long?’ ” Doctors had never implanted a lab-grown bladder into a human patient before. “We really did not know what to expect long term.”
Today, the bladders have not moved beyond phase two clinical trials, 14 years after they were first implanted in patients.
Trailblazing — for all its connotative speed — needs to be done slowly.
Explosive Growth Meets Slow Moving Regulations
The promise of lab-grown organs is enormous. Just in the Unites States, more than 120,000 people are currently on organ-transplant waiting lists, and only 19,000 transplants took place in the first eight months of 2013. Since the 1990s, the gulf between the number of transplant patients and the number of organs has only grown wider.
After a patient is approved for a transplant, there are still dangers. Fifteen to 20 percent of kidney recipients will face organ rejection within five years of implementation. Twenty-five percent of heart transplant recipients experience some rejection in the first year after surgery.
Regenerative medicine can help solve these two problems: Grow organs on demand to increase supply, but also grow them from the host’s cells, to mitigate complications.
Luckily, innovation is exploding.
Stem cells are a relatively recent invention, first cultivated outside the body in the 1990s. Since then, the field has grown by leaps and bounds. Now, we can coax an adult cell into an embryonic-like state, or what’s known as a pluripotent state, which means it can transform into many different types of cells.
That work won a Nobel Prize in 2012. “Clearly, that’s had a huge impact on the field,” says William Wagner, director of regenerative medicine at the University of Pittsburgh. “A lot of people are looking to those cells as a potential source,” as the debate around embryonic stem cells has become clinically irrelevant. With such technologies, labs have grown mildly functioning kidneys and beating hearts for rats. For humans, lab-grown skin and cartilage are coming into mainstream use. We can grow noses on foreheads.
More than the cells themselves, the structural engineering science is also bouncing ahead. Three-dimensional printers can build biological structures one cell at a time, crafting the delicate organ structures of the body. One of the more exciting developments is the ability to wash an animal or human organ of all its cells to reveal the underlying structure. Then, researchers reanimate the organ with completely new cells, specific to the host — bringing dead tissues back to life.
But here’s the key disclaimer: “If it can be done in a mouse or a rat, extrapolating that to a human, the number of pitfalls, and the number of assumptions that happen in that, particularly in the mouse model, are huge,” Wagner explains. In 2006, Atala’s bladders were, in terms of the clinical-approval timeline, worlds beyond, let’s say, a lab-grown pancreas derived from testicle cells that could possibly cure diabetes. Any proof of concept in an animal is decades away from widespread use, and that’s assuming it will be viable for humans at all.
Maybe We Can’t Grow a Heart, But Can We Heal One?
In the near future, we’ll be more likely to see stem-cell-based therapies rather than outright organ replacement.
“We’re shooting at the moon in trying to make a heart or make a liver, and you discover so many things along the way that sometimes you don’t want to go to the moon after all,” Wagner says.
For instance, instead of wholesale organ replacement, doctors are finding that simply injecting an organ with certain stem cells can produce a healing effect. A large number of ongoing investigations expect cell therapy to eventually change the treatment of any given chronic condition, Wagner says. Maybe in a decade, he says, they will yield therapies for conditions such as as heart disease and stroke. And perhaps, later on, for Alzheimer’s and Parkinson’s. In 2013, a published clinical trial that involved injecting cells into diseased heart tissue showed that “every patient in the stem-cell-treatment group improved.”
“Are they going to be cures? Probably not in a 10-year time frame,” Wagner says. “But they are going to show enough benefit that they would be adopted, opposed to what’s currently done clinically.”
And then there are practical concerns to growing entire organs. It may not prove to be a viable business model to tailor-make organs for individual patients. “Private industry is going to have to raise millions and millions of dollars not around the science, but around the practicality,” Wagner says. “Specifically, what patients are you going to treat, how many per year, what’s your reimbursement rate going to be, how long it’s going to take to get through the FDA. All these practical regulatory business concerns — and often that’s what is putting a barrier between an interesting report that you read about a study in rodents or even in pigs and if it ever gets translated to humans.”
But the Baby Steps Still Matter
If, today, we built a human body using only lab-grown parts, the anatomy would be sparse. The body would have a bladder, a trachea, some blood vessels, some muscle fiber, skin, tear ducts, and a urethra — maybe a sphincter.
These are the simpler organs of the body. There are four levels of organ complexity, the first being flat surfaces like skin, the second hollow tubes like trachea, the third hollow structures, like the bladder and stomach, and the fourth solid structures, such as the liver and lungs. “Up to this point, we’ve been able to implant the first three types in patients,” Atala says, “but we have not yet implanted solid structures in patients. That’s still years away.”
One of the barriers to that next step is feeding those organs. A kidney requires a lot of vessels to keep functioning. And not just big arteries, but tiny capillaries to feed all the cells. Over the summer, Johns Hopkins researchers found a way to grow networks of tiny human blood vessels in mice, the type that could someday feed a lab-grown kidney or other complicated organ, or to simply repair capillaries damaged by diabetes. “This is why we are very excited about it — because the vasculature is relevant for almost any tissue type,” Sharon Gerecht, a researchers on the study, says. Still, the field remains in infancy.
“You have to remember, the field started with mouse cells in 2006, so it is pretty young,” she says. “We still don’t know exactly how pluripotent they are. Do they remember that they were diseased and old before? We still don’t know this, and it will take time for research to find out.”