Fight Aging!

The ability to cryopreserve and thaw organs via vitrification, without ice formation and significant tissue damage, allowing for indefinite storage time, would go a long way towards simplifying the logistics and reducing the costs of present organ donation and future tissue engineering of organs for transplantation. Cryopreservation via vitrification also offers the possibility of indefinitely storing the terminally ill and recently deceased until such time as medical science advances to the point of restoration. This has been practiced for several decades by the small cryonics industry.

Cryonics is a long shot, but better odds by far than the grave. The challenges to progress in cryonics seem largely technical: it is presently possible to vitrify organs, but thawing them safely is another story entirely. Scaling up the reliability of vitrification processes to the whole body continues to be a work in progress, even while practiced by the cryonics community. The funding for technological progress in this field remains sparse, a situation that could be remedied by an industry of organ cryopreservation associated with donation and transplantation. Given a world in which it is routine to vitrify and thaw donated organs, it will be far easier to accept the cryopreservation of terminally ill individuals in hope of a better, more capable future, and more funds will be drawn to that goal.

Cryopreservation has multiple and important applications, particularly in medicine. The fact that it can significantly slow down all biochemical reaction kinetics renders cryopreservation highly attractive as a means to preserve organs and therefore facilitate the transplantation process. The lack of organ availability constitutes a major challenge and a significant medical burden for society. According to the World Health Organization (WHO), only 10% of the worldwide need for organ transplantation was met in 2010. The lack of transplantable organs stems partially from a shortage of suitable donated organs, but more importantly from the lack of preservation capability. Although the number of transplanted organs is much lower than what is actually needed worldwide, it was estimated that approximately two thirds of potential donor hearts are discarded.

Kidneys and hearts have been the most widely studied organs, but neither has been consistently recovered after cooling to temperatures lower than -45 °C. Nevertheless, sporadic survival of kidneys has been claimed after cooling to lower temperatures. Along those lines, researchers reported success in vitrifying a rabbit kidney at -130 °C which was rewarmed using a special conductive warming technique combined with perfusion. After warming, the kidney was transplanted into a recipient rabbit that lived for 48 days with a working kidney before being sacrificed.

Cryopreservation is an interdisciplinary endeavour between medicine, biology, bioinformatics, chemistry and physics. The main challenges still to overcome are scaling up current methods to larger volumes and complex tissues. The larger the organ, or tissue volumes to be vitrified, correspondingly more time is required to cool and warm the organ. Not only thermal conductivity is an issue here but cryoprotective agent (CPA) viscosity limits for perfusion systems play a role. The protocols for cell lines, or even small tissues, such as sperm, eggs, or corneas, cannot be replicated in larger human organs, which necessitate toxically high CPA concentration to inhibit ice formation during the longer time spent between the melting temperature and the glass transition temperature, and of course gives more time for toxic insults to accumulate.

The best techniques to get around these problems in small tissues use combinations of CPAs to reduce toxic effects of any single agent, using CPAs with weak water interactions to minimise disruption of hydration layers around biomolecules, using CPAs with mutual toxicity neutralisation effects, and reducing penetrating CPA concentrations by adding non-penetrating CPAs and ice blockers. Nonetheless, little is known about the mechanisms at work.

The challenges in cryobiology are not insurmountable. Future research will focus on ever more complex ways to prevent ice formation and mitigate cryoprotectant toxicity; novel cryoprotectants which exert disproportionately large cryoprotective effects compared to their concentration, in silico molecular modelling, and enhanced understanding of the processes that occur during cryopreservation will all be employed. One could envision a universal cryoprotectant solution, suitable for use in a range of tissue types, and physical advancements enabling high cooling and warming rates, or the manipulation of ice formation for large volume vitrification or freezing.

Whilst the concepts have been long known, the dedicated field of cryobiology dates back only around 70 years. In that time, it has advanced from freezing spermatozoa using glycerol, to vitrifying tissues, and even small organs using complex multi-component solutions. This is remarkable progress given that cryopreservation is as yet a relatively niche field of study, without garnering much attention in schools or undergraduate courses and utilising a fraction of the funding which is allocated to other causes. As such, there are still many opportunities that lie ahead, from short-term improvements in transplantation biology, to ambitions that may once have been viewed as science fiction, such as the building of organ banks or long-term suspended animation.

Link: https://doi.org/10.1186/s12915-021-00976-8