By Kiona Smith-Strickland
Paolo Macchiarini
Staffan Larsson
May 29, 2013 4:12 PM Text Size: A . A . A
Why study the trachea?
It started many years ago when I was a resident and I did my Ph.D. on organ and tissue transplantation. Crazy as it might be, the trachea was the only organ that was not transplanted. The fact that so many children during my clinical rotation were dying of airway diseases without any possibility of being treated triggered my interest in tracheal transplant. How do you create a trachea from stem cells?
It's a long process. We will need to know exactly what the [three dimensions] of the trachea are that the patient requires. Then we need to calculate how many cells we would need for seeding the trachea with the patient's own stem cells and build a specifically designed bioreactor. The trachea, when it is transplanted, is seeded with nonembryonic cells (so-called mononuclear cells) using a bioreactor where the cells attach to it and proliferate. Once transplanted, these cells locally become viable trachea cells. They stay for days and weeks, and when they die, they give a signal to the other cells. Cells in the blood can be recruited and then further differentiate. We help the human body to boost the regeneration by giving growth factors for a period of two weeks post-transplant. Hannah Warren was born without a trachea. How common is this condition?
It's very rare. It's one out of every 50,000 births. The problem is that almost 100 percent [of patients] die by 6 years?the longest survival has been 5 or 6 years. So it's a very rare but lethal disease. What other kinds of patients are candidates for this surgery?
Most have had benign diseases of the airways, but a few have had malignant tumors, so tumors are an indication. You had to get authorization from the Food and Drug Administration to perform Hannah's surgery.
This still is an experimental therapy, so basically you cannot get permission for the routine cases. You need to do this only in the worst scenario for patients who have been maximally pretreated through surgeries or other types of treatments. To get authorization for clinical trial, you need to provide the evidence that this technology is safe and effective enough in animals and in a small-case clinical series. Once you have provided the evidence, then the national authority usually grants the trial. You performed a nine-hour trachea transplant surgery on a 2-year-old. What was that like?
Hell. It was very complex because, despite all the preoperative investigations, you usually find something that you do not expect. Are these transplants risky?
At least the patients we have [treated] were patients where this transplant was the last resort, and this is the reason why the complication rates are higher [than with other types of surgery]. The outcome clearly is influenced by surgical complication rate and the primary disease, because we have patients who died from the tumor irrespective of the transplant. Hannah will outgrow this trachea in five years and need a replacement. Is there a way to build a trachea that might grow with the patient? Are organs grown from stem cells different in any other way?
I don't expect that the trachea would grow. It would be wonderful, but in five years, we will have saved her life and the routine transplant will be much easier, so there will be no comparison with the one she had. We are working on [organs that grow], yes. [They] do not look different, and probably do not even behave differently. Has the controversy over embryonic stem cells impacted your work with nonembryonic stem cells?
Not necessarily, because I think that scientists should be open and should not take into account the controversy. My point is that if science is done, it should be regulated by strict guidelines and done without political interference. If we can have just one single patient saved, a child or an adult, all this controversy is just nonsense. We just need to respect the regulations, the rules, and do scientifically sound research. What's next?
o extend what we have done in other types of tissues, like the diaphragm, and treat not-treatable disease not by replacing the organ but by doing cell therapy?that would be my dream. You could use your own stem cells to restore the function of an organ that has lost its function because of disease. Basically, the framework is still there. We just need to restore the cells that make this organ live. Bret Bielema sons of anarchy adriana lima victoria secret fashion show SEC Championship Rick Majerus Cotto vs Trout
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