It's 10am at the Hospital Clinic of Barcelona and one of the surgeons is doing his rounds. He’s stopped at the bed of a patient who for months has been fighting for breath whenever she walks anywhere. Things have got so bad recently that she can barely make it from her bedroom to the living room. A chest scan reveals that she’s got a serious condition called pulmonary hypertension. The blood vessels in her lungs have thickened, so the oxygen she breathes in struggles to get into her bloodstream.
But this is 2019, and a new technique has just come into mainstream use that could help her out. Just an hour after diagnosis, she’s in an operating theatre having stem cells injected into the airways of her lungs. The procedure is completed in minutes. Over the coming days, things start to look much better for the patient. She’s now walking the length of the ward without getting breathless and her doctors say she’ll make a full recovery.
This is the dream of Professor Paolo Macchiarini, who works at the hospital. He came to prominence last year when he performed the first organ transplant using a patient’s own stem cells. That patient was Claudia Castillo, whose windpipe was damaged by TB. Her stem cells were used to grow a new piece of windpipe to replace the damaged section, without risk of rejection.
Macchiarini has high hopes for stem cells – cells with the power to turn into many of the specialist cells in the body, such as muscle and nerves. In fact, he’s already tried injecting them into mice lungs to treat hypertension – and it worked. But his ideas don’t end there. The body is actually littered with stem cells and Macchiarini says that if you could find something to trigger them into action – a magic bullet – they could repair the organs, eliminating the need for a transplant in many cases. Crucially, Macchiarini says he thinks he knows what that magic bullet is.
And Macchiarini isn’t alone in his hope of finding new ways to restore organs. Professor Anthony Atala, one of the world’s leading tissue regeneration experts, is looking at the solution from an entirely different perspective. He thinks the humble ink jet printer could hold the answer.
Right now, in 2009, the outlook wouldn’t be too rosy for our hypothetical patient. Drugs would suppress her symptoms to an extent. But not much. And instead of a simple injection, she’d be on the organ transplant list, waiting for a new pair of lungs. The chances are, she’d probably be waiting a long time. In fact, she may die there. In the UK there are many successful transplants each year – there’s no doubting that. But about 400 people on UK waiting lists simply run out of time.
Dr David White, a British-born scientist who now works in Canada, has pretty strong views on the situation. “Transplantation is a complete failure,” he says. “And the reason it’s a failure is that there aren’t enough organs to transplant.
One obvious solution to this lack of organs for transplant is to use body parts from animals. It may sound unsavoury, but the idea of xenotransplantation has already been tried on more than one occasion.
Back in 1984, a five-pound infant known only as Baby Fae had a baboon’s heart placed in her chest at the University Medical Center in California. She died 20 days after the transplant when her body launched a massive immune response.
Despite early setbacks like this, there’s still interest in organs taken from animals. A World Health Organisation meeting in China last November resulted in the so-called Changsha Communique – a document that will eventually guide the practice of xenotransplantation globally. And in the US, pig hearts have already been transplanted into baboons, paving the way for trials in humans. Much of the research is focused on genetically altering the pigs so their organs don’t provoke the kind of immune response Baby Fae experienced.
Rather than transplanting a complete animal organ, White’s area of interest is in transplanting parts of organs. He is looking at taking insulin-producing cells from pigs and transfering them into diabetics. The cells, called Islets of Langerhans are taken from the pig’s pancreas and places inside the patient’s abdomen, to help regulate their blood sugar level.
White, who works at the Robarts Research Institute in Canada, has a few clever tricks up his sleeve to make sure the patient’s immune system doesn’t go into overdrive and launch an attack on the pig cells. The islets are mixed with another type of cell called Sertoli cells that are found in pig testes. These act as guardians for the insulin producers, preventing an attack by the patient’s immune system. White is hoping to get permission from the US authorities to start clinical trials of the procedure in the next 12 months.
But won’t people feel squeamish about having cells from pigs inside them? “I’ve been asked this question many times,” says White. “I think someone who is not diabetic may well raise the yuk factor. But we have been using pig insulin to treat diabetes since 1923 and no-one is squeamish about that.
Think before you print
But instead of taking organs from animals, why don’t we just make our own from scratch? That’s where Professor Atala’s ink jet printers come in. He uses a printer that works with living cells rather than ink.
The printer head has been modified so it moves vertically producing a 3D structure, one layer at a time.
“We can print a complete solid organ, such as a heart, but in miniature,” says Atala, director of Wake Forest Institute for Regenerative Medicine in North Carolina. “The idea of 3D printing has been around for a long time in things like CAD [computer aided design]. All we’re doing is applying the technology that’s already out there to biological systems.”
Once they have been printed using mouse or donated human cells, these miniature hearts spookily start beating. The biggest challenge is keeping all the cells supplied with nutrients. And it’s this problem that’s causing most of the head scratching at Wake Forest.
Atala’s extensive tissue-growing know-how will be tapped into during a military project that has some mind-blowing aims. Last year the US Department of Defense announced the creation of the Armed Forces Institute of Regenerative Medicine (AFIRM). Aimed at helping troops who’ve been injured in battle, it will look at how to regrow skin, muscles and tendons – even ears, fingers, arms and legs (see ‘Grow your own,’ above).
One of Atala’s colleagues, Dr James Yoo, will carry out research for AFIRM. “One approach we are looking at is utilising the body’s ability to regenerate,” says Yoo. “There are stem cells in almost every organ and we are trying to find a way to activate them to regenerate tissue. It could be used for both internal and external organs [fingers and toes, for instance]. The key is to find the right cues.”
That’s where Macchiarini’s magic bullet comes in. But what is this mystical substance that could kick-start the body’s stem cells into action so they repair damaged organs? Well, anyone with an interest in professional cycling will have heard the name – erythropoietin, or EPO. For cyclists it has the handy (but outlawed) effect of boosting the number of oxygen-carrying red blood cells in the blood. Atala believes the hormone could also be a signal to stem cells to take action.
If he’s right, then an EPO injection – along with, perhaps, an implant of a few extra stem cells for good measure – could be enough to repair a faulty heart, lung or liver. The EPO would know where to act by spotting inflammation.
No miracle cures
Professor Andrew George at Imperial College London researches techniques to reduce a patient’s immune response to transplants – both conventional ones and those involving xenotransplantation. He says it’s important to manage people’s expectations of the alternatives to conventional transplants – whether they are stem cells, printed organs or tissues from animals. “When I started work on monoclonal antibodies in the mid-’80s, they were going to cure everything – heart disease, acne, cancer, flatulence – everything,” he says. “Anyone with a white coat and a syringe could get a grant to work on them. When I came back from the States in 1992, you could not get money to work on them. Now they have important applications, such as herceptin. But they are only used in certain areas.”
George thinks that stem cells could follow the same pattern. At the moment, they’re the cure-all miracle of tomorrow. In five years’ time maybe they’ll be the latest medical white elephant. And only five years after that will we have a realistic appraisal of what they can do.
“We went through a period when xenotransplantation would do everything and we’d have organs coming out of our ears,” he says. “Then there was a period when we said it would do nothing. Now we’re at the stage of saying, ‘Where can we apply it?’ It’s about managing hype, which is something we’re not very good at.”