Freezing (and then carefully warming) donor organs breaks the organ transplant time barrier (for rats, for the time being)

 Here's a note in Nature Reviews Nephrology pointing out the longer term promise of the recent successful freezing, thawing, and transplantation of rat kidneys.

Cryopreservation breaks the organ transplant time barrier by Marlon J. A. de Haan & Ton J. Rabelink, in Nature Reviews Nephrology (2023)

"The pressing issue of organ shortages for transplantation is fuelled by the rising incidence of kidney failure and the declining quality of organs from an ageing donor pool. However, the main bottleneck in organ transplantation is time; indeed, the current clinical standard for kidney preservation necessitates immediate transplantation following organ recovery1. This urgency often results in suboptimal matches between donors and recipients. Cryopreservation has emerged as a potential solution to this challenge. Such an approach would enable organs to be preserved in a suspended state for extended periods and ready for transplantation on demand. The prospect of long-term banking of cryopreserved organs holds promise for transforming organ transplantation into an elective procedure, thereby enhancing donor–recipient matching, improving equity in access, optimizing patient preparation, refining transplant tolerance protocols, increasing organ utilization and improving graft and patient survival. However, even though cryopreservation has successfully been used to store human embryos, extending the process to preserve whole organs has remained a scientific aspiration — until now. A study by Han et al. introduces an approach to cryopreservation that seemingly extends the shelf life of organs indefinitely2."

...

"By rapidly cooling rat kidneys to –150°C, Han et al. were able to halt the biological clock of the organs, effectively inducing a glass-like state — a process known as vitrification2 (Fig. 1). Specifically, the researchers perfused a cocktail of cryoprotective agents (CPAs) and iron oxide nanoparticles into the organ’s vasculature, which they followed by rapid cooling to ultralow temperatures to achieve a state of vitrification. This vitrified kidney, with its hard, smooth, glasslike appearance, was then transferred to a –150°C freezer for long-term banking. When these kidneys were later rewarmed and transplanted into nephrectomized recipients, they regained life-sustaining renal function. The rewarming stage poses more challenges to the process of cryopreservation: it requires both speed to avoid ice formation during devitrification and uniformity to prevent thermal stresses and mechanical cracks. Here, the iron oxide nanoparticles had a crucial role. Placing the vitrified kidney in a coil that generates electromagnetic fields activates these nanoparticles, generating heat. This innovative approach enabled rapid rewarming at an impressive rate of approximately 72 °C per minute throughout the entire organ, ensuring uniform warming rather than limiting warming to the organs’ surface. This ground-breaking milestone marks an extraordinary achievement in ‘reviving’ a complex organ like the kidney and is the culmination of decades of research into methods to prevent the destructive formation of ice during the cooling process, minimize toxicity from CPAs, and enable fast and uniform rewarming3.

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Wednesday, June 28, 2023

Freezing, thawing and transplanting a rat kidney: a first step towards organ banking