Vitrification and nanowarming enable long-term organ cryopreservation and life-sustaining kidney transplantation in a rat model

Abstract

Banking cryopreserved organs could transform transplantation into a planned procedure that more equitably reaches patients regardless of geographical and time constraints. Previous organ cryopreservation attempts have failed primarily due to ice formation, but a promising alternative is vitrification, or the rapid cooling of organs to a stable, ice-free, glass-like state. However, rewarming of vitrified organs can similarly fail due to ice crystallization if rewarming is too slow or cracking from thermal stress if rewarming is not uniform. Here we use “nanowarming,” which employs alternating magnetic fields to heat nanoparticles within the organ vasculature, to achieve both rapid and uniform warming, after which the nanoparticles are removed by perfusion. We show that vitrified kidneys can be cryogenically stored (up to 100 days) and successfully recovered by nanowarming to allow transplantation and restore life-sustaining full renal function in nephrectomized recipients in a male rat model. Scaling this technology may one day enable organ banking for improved transplantation.

Novel Hybrid Ferromagnetic Fe–Co/Nanodiamond Nanostructures: Influence of Carbon on Their Structural and Magnetic Properties

“…This nanohybrid system, whose synthesis and characterization are reported here for the first time in the literature, exhibits structural and magnetic properties that can be exploited in contemporary technological applications such as biomedicine [50]. Moreover, developing and analyzing the martensitic type Fe-Co phase in these samples could serve as a guide to unveil the conditions and means of producing such tetragonally distorted structures, thus further pushing the effort to deploy new non-rare-earth-based hard FM materials.…”

A Low-Cost, Tabletop LOD-EPR System for Nondestructive Quantification of Iron Oxide Nanoparticles in Tissues

“…A general range of 0.01−100 mg Fe/mL is assumed for nanowarming based on the lower range of IONP concentrations that have safely remained in kidneys postwashout 9 and the potential upper range of IONP concentrations that could be used with more recently developed IONP coatings for nanowarming. 10 While a specific accuracy tolerance for nanowarming has not yet been established, it is an area of active study, as the IONP Fe concentration is directly proportional to the warming rate.…”

“…While a specific accuracy tolerance for nanowarming has not yet been established, it is an area of active study, as the IONP Fe concentration is directly proportional to the warming rate. However, for reference, a tolerance for rewarming of 72 ± 8 °C/min was achieved in the kidneys that were successfully vitrified, nanowarmed, and transplanted for 30 days, with an estimated rewarming threshold of 50 °C/min . Further study is needed to establish the precise threshold for failure and appropriate tolerances to mitigate the associated risks; however, the required accuracy for quantifying the IONP Fe concentration will be reflective of this analysis.…”

Engineering Magnetic Nanoclusters for Highly Efficient Heating in Radio-Frequency Nanowarming

“…Magnetic nanoparticles have emerged as a promising platform for nanowarming, a technique that leverages these nanoparticles to generate heat under an alternating magnetic field, thereby facilitating rapid and uniform heating of cryopreserved biological samples. − Their potential to overcome the limitations of traditional convective rewarming methods has been demonstrated across tissues and organs, including rat hearts, livers, and kidneys. − While previous work mainly focused on establishing the fundamental principles, feasibility, and initial protocols for nanowarming, the work used commercially available iron oxide nanoparticle cores and rational optimization of intrinsic nanoparticle properties such as size, assembly states, and surface coating to boost their heating performance remains less investigated. − …”