Pig Kidneys Remain Functional After Vitrification with Iron Oxide Nanoparticles, Rewarming, and Transplantion
Recovery and transplantation of organs following vitrification using cryoprotectant is an important step along the road to the future technological capability of whole body vitrification and recovery - and recovery of those individuals already preserved at low temperature by the cryonics industry. It is particularly important because it is a highly desirable capability for the organ transplant industry, and thus a way to bring significant funding and credibility to the endeavor of cryonics, the preservation of people for future revival. Scaling up vitrification and rewarming to human sized organs has been a major challenge on several fronts, such as effective perfusion of cryoprotectant in large tissues, performance of the cryoprotectant, consistent warming of deeper tissue in a large vitrified mass, and so forth. It is much easier to vitrify and reward small tissue samples than large ones. Here researchers report success in pig kidneys, albeit using an approach to rewarming that requires preparation of the organs prior to vitrification, and thus cannot be applied to tissues and people preserved prior to its introduction. Nonetheless, it is an important step forward.
Vitrification and nanowarming have enabled long-term preservation and transplantation of rodent kidneys but have not been demonstrated at the scale of clinically relevant organs. Here we show that vitrification and electromagnetic nanowarming enable long-term cryogenic storage and functional recovery of human-scale porcine kidneys. Kidneys 100-fold larger than previously nanowarmed kidneys were successfully recovered after storage at -150 °C for up to one year. A new cryoprotectant formulation and multithermic perfusion strategy enabled ice-free vitrification at cooling rates achievable in large kidneys, while controlled cooling with annealing and staged volumetric nanowarming limited thermal stress and enabled rapid rewarming without cracking.
Nanowarming was developed to overcome the limitations of surface-based rewarming. Silica-coated iron oxide nanoparticles distributed through the vasculature before vitrification generate heat when exposed to an alternating electromagnetic field, enabling rapid volumetric rewarming throughout the organ.
Rewarmed kidneys demonstrated vascular, metabolic, and excretory function during normothermic perfusion, with limited histological injury, and reperfused homogeneously and produced urine immediately after transplantation. Functional recovery approached static cold storage outcomes across several measures and was similar to that of kidneys exposed to cryoprotectant alone, suggesting minimal additional functional injury from vitrification, cryogenic storage, and nanowarming. These findings overcome major scale and storage-duration barriers to organ cryopreservation and establish a path toward organ banking on timescales far beyond those of conventional preservation.