9. The grand challenge of true organ banking and the current state of the art

Abstract

Although it is instructive that many complex organisms can survive freezing and thawing in nature, none of them are mammals, many of them can’t survive in the frozen state for years on end, most of them are smaller than mature human organs, and most of them can’t survive if frozen in the summer. For organ banking to be practical, we must exceed these limitations of nature, enabling large mammalian organs to be banked indefinitely, at any time, at temperatures below those encountered by life under natural conditions, and without the benefit of millions of years of evolution to reconcile all of the problems of doing so. This is indeed a grand challenge, but one we can now have every hope of achieving. Many studies have shown that while some ice formation can be tolerated in mammalian tissues and even in some organs, it is also clear that ice can be quite damaging, and is probably best avoided. Fortunately, mammals can survive supercooling, and by adding cryoprotectants, we can now extend supercooling in isolated organs all the way to the glass transition temperature, thus in principle enabling ice-free cryopreservation in the vitreous, or glassy, state. However, tolerating the cryoprotectants and tolerating the cooling step itself represent grand challenges in and of themselves, because vitrification requires extensive dehydration of the whole organ, and cooling leads to the ill-defined problem of “chilling injury.” These problems have been controlled to a remarkable extent by improvements in vitrification solution design and perfusion technique, and as a result, we may now be poised at the brink of success with at least one model system, the rabbit kidney, and one kidney has already been vitrified, rewarmed, and transplanted with indefinite life support thereafter. However, the following problems remain. First, tolerance of the rabbit kidney to the requisite cryoprotectants is not adequately consistent, indicating that further means of reducing toxicity are still needed. Second, chilling injury will require more detailed examination in the whole organ. Third, although fracturing can clearly be avoided, careful investigation is still needed to determine if thermal contraction of organs might be damaging to them independently of fracturing and conventional chilling injury, a question that to date has not been addressed at all. Fourth, it is necessary to prove that whole organs can be stored for extended times near the glass transition temperature, which is necessary for minimizing the risk of fracturing. Fifth, the successful application of new electromagnetic warming methods to actual banked organs remains to be demonstrated. Sixth, every organ or tissue composite clearly has its own unique advantages and disadvantages for vitrification, and a vast amount of work remains to be done to master the vitrification of them all. On the positive side, there is a world of opportunity ahead in the area of organ “rehabilitation” after transplantation. In summary, although the challenges of stopping biological time in something as complex as a whole human organ are profound, the promise of success is real, and the road ahead is full of exciting opportunities.