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New method strips lungs of old cells in three hours
12 July 2013
A faster and more effective method of preparing organs for transplant has been successfully tested on rat and sheep lungs. The procedure, which took a few hours rather than the few weeks normally required, used detergents to strip the lungs of their old cells, leaving the organ’s microarchitecture intact and ready for use. The method, developed by a team led by the UCL Institute of Child Health and published in the journal Biomaterials, is a further step forward in the quest to provide transplants free from the risk of rejection.
People who receive transplants usually need to take immunosuppressants to reduce the risk of their body rejecting the new organ, which may still contain some of the donor’s old cells. Scientists have been testing ways of ‘washing’ organs to completely remove donor cells and thus eliminate the need for anti-rejection therapy. However, the harsh detergents and long washing periods used for more complex organs – deemed necessary to thoroughly ‘cleanse’ their intricate infrastructure – have often damaged the remaining tissue, known as the extracellular matrix (ECM), and stripped it of essential components such as growth factors needed to kick-start the organ after transplantation.
The new decellularization or cell-stripping method, developed by an international team led by the UCL Institute of Child Health and Great Ormond Street Hospital, used gentler detergents to flush rat lungs while they were intermittently inflated – mimicking the process of respiration or breathing while the lung was being washed.
The cleansed organ was then injected with a dye which revealed the capillary network or blood vessel system to be intact. Inspection with an electron microscope showed an intact alveolar network, with no evidence of collapse or tearing at the junctions where the lungs exchange carbon dioxide and oxygen. Further tests revealed the presence of ECM components such as collagen and elastin, essential for the organ’s function.
The study, funded by Great Ormond Street Hospital Children’s Charity, found that the method worked on sheep as well as rat lungs, meaning it could be scaled up to human-sized organs. The lungs were also ready in three hours compared with conventional processes that can take up to five weeks.
Dr Paolo De Coppi, UCL Institute of Child Health and lead author of the study, says: “The method developed in our study takes us one step closer to being able to provide ‘lab-grown’ lungs for transplants. The lung has a particularly fragile microstructure and its preservation requires a mix of gentle washing with intermittent flushing, mimicking what normally happens during breathing. The advantage of our method established in rats is that we have found it to work equally well in a larger animal model, an adult sheep lung, which has a similar structure to the human lung. Thus, we move closer to the day when donated human lungs can be used as scaffolds for tissue-engineering new ones using a patient’s own stem cells.
“The next stage of our work will be to test this method of washing on human lungs in our laboratory. After they have been stripped of their old cells, we will ‘seed’ them with new cells to see if we can ‘grow’ a human lung ready for transplant, free of the risk of triggering rejection. If this proves successful, we will test the new transplants in animal models and eventually, in humans.”
Elliott, Medical Director at Great Ormond Street Hospital and co-author
of the study, says: “I have been doing lung transplants for almost 25
years and know first-hand the anxieties that the risk of rejection bring
to patients and their families. But the burden of the drugs they have
to take, and the side effects they have, is also huge. This work
provides early hope that we might be able to transplant organs without
such powerful drugs and improve the lives of many.”
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