16 March 2017

A new method of storing donor lungs

A group of researchers from Columbia University, working under the leadership of Professor Gordana Vunjak-Novakovic and associate Professor Matt Bacchetta, for the first time managed to maintain the full functioning of the lung outside the body for 36 hours. The complex supporting system developed by them makes it possible not only to preserve the viability of donor lungs, but also to restore violations of their functions caused by ischemic injuries resulting from lack of oxygen during organ transportation.

Cross-circulation.jpg

Photographic, radiographic and thermographic images of damaged lungs restored using an extracorporeal cross-circulation platform. The lungs subjected to this procedure for 36 hours demonstrated normal levels of all pulmonary functions: perfusion, ventilation and gas exchange. Photo: Gordana Vunjak-Novakovic.

The authors were prompted to work in this direction by an acute shortage of donor lungs, the transplantation of which remains the only effective method of treating the final stages of various diseases. In addition to the shortage of donor organs, there is another problem – outside the body and during transportation, the lungs lose their functionality very quickly, therefore, out of 5 withdrawn donor organs, as a rule, only 4 are suitable for transplantation.

Instead of trying to grow new lungs, the researchers decided to develop strategies to improve the quality of donor organs. One of the potential approaches to solving this problem involves the use of cell therapy – replacement of damaged cells with therapeutic cells of the recipient of the donor organ. Theoretically, this approach is applicable to low-quality donor lungs that are not suitable for transplantation, but there is one serious problem: the period during which existing methods allow maintaining the viability of the lung outside the body is not long enough for therapeutic cells to begin restoring its functions.

As often happens, unmet clinical needs have inspired researchers to come up with new ideas and develop new technologies. The authors suggested that "cross–circulation" - a forgotten surgical procedure used in the 1960s to exchange blood between two patients – is capable of maintaining the viability of organs outside the body for a long time by supplying them with critical systemic and metabolic factors that are not provided by existing technologies.

An accelerated (1 frame per minute) survey of the lung located outside the body, the recipient's vital signs (upper right panel) and perfusion data during the 36-hour cross-circulation procedure.

According to Professor Vunyak-Novakovich, the lung is a complex masterpiece created by nature. This organ consists of 40 types of cells, and the gas exchange surface area provided by it reaches 100 square meters, that is, approximately equal to half the area of a tennis court.

Therefore, during the development of their cross-blood supply platform, the authors faced many difficulties. So, to prevent the outer surface of the lung from drying out and maintain normal body temperature, they developed a humidification system with the function of maintaining temperature, as well as a container for an organ with circulating warm water to reproduce the conditions of the chest cavity.

The next task was to create a system for perfusion. To ensure adequate blood flow in the donor lungs during the cross-circulation procedure, the authors have developed new devices and techniques, including an approach consisting in using the donor vessel as a "bio-bridge". The result of the work was the creation of a dynamic system that allows you to adjust the hydrostatic pressure and maintains blood flow, regulated by pressure on the principle of feedback. They have also developed technologies for targeted delivery of drugs and cells to different regions of the lungs, carried out under visual control without the need for multiple biopsies.

Using a clinically significant pig model of their cross-circulation system, the authors demonstrated the possibility of maintaining the normal functioning of healthy donor lungs for 36 hours, as well as the possibility of restoring the functions of organs damaged by ischemia. At the same time, the total duration of the lungs being outside the body, including the period of cold ischemia, averaged 56 hours.

A long period of being outside the body provided the possibility of multi-level therapeutic interventions. Upon completion of the cross-circulation procedure, the parameters of the donor lungs not only met all the transplant criteria, but also exceeded them. The recipients tolerated the procedure well without significant changes in physiological parameters throughout the 36-hour period.

The developers believe that the new platform they have created can be used not only to preserve and restore donor lungs, but also to improve the quality of other extremely popular donor organs, including the liver and kidneys. They have already started working in this direction.

Article by John D. O'Neill et al. Cross-circulation for extracorporeal support and recovery of the lung is published in the journal Nature Biomedical Engineering.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on materials from Columbia University: New Method Rescues Donor Organs to Save Lives.

16.03.2017


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