Bringing nature back: using hibernation to reboot organ preservation

Abstract

Recently, organ transplant therapy has received a major boost from a change in perspective – a move away from damaging, cold static organ storage to the use of warm normothermic perfusion. The concept for warm preservation is one that has been borrowed from Nature, and it is only fitting that we go back to the wild for more ‘tricks’ to further improve warm organ stabilization. Current warm preservation strategies are designed to mimic natural conditions in the human body as closely as possible, but what if we could mimic these conditions while simultaneously inducing a reversible state of torpor that would further extend the viability window of donor organs? Indeed, the original driver for using cold organ storage was its ability to strongly reduce metabolic rate many‐fold when organs were cooled from 37 to 5 °C. Herein, we discuss the adaptations that allow warm hibernators such as bears and lemurs (fellow primates) to naturally depress their metabolic rate and retreat into states of suspended animation, and how these can be applied to improve organ transplant therapy. Can we look to Nature for instructions to induce torpor in human organs? This article discusses the possibilities.

Heterothermy as the Norm, Homeothermy as the Exception: Variable Torpor Patterns in the South American Marsupial Monito del Monte (Dromiciops gliroides)

“…This is coincident with what was observed in heterothermic birds and mammals in unpredictable environments (e.g., hummingbirds and nig=htjars), which express torpor when incubating and also in mammals of the three orders (i.e., monotremes, marsupials, and placentals), which express torpor during pregnancy and lactation (reviewed in McAllan and Geiser, 2014 ). Similarly, torpor at room temperatures is known to occur in rodents ( Grimpo et al, 2014 ), bats ( Johnson and Lacki, 2014 ), and primates ( Hadj-Moussa and Storey, 2019 ) as adaptations to seasonally dry habitats. What is intriguing with D. gliroides is that it lives in a temperate rainforest characterized by humid and mild temperatures, where the water economy does not seem to be a problem.…”

Identification of conserved gene expression programs activated in multiple modes of torpor across vertebrate clades

“…Identification of conserved gene expression between torpor in more basal animals and those discussed in this paper could push back the date of the evolution of torpor and generalize the torpor state to include pauses in development. An additional goal of torpor research is to identify effective methods of inducing torpor in nonheterothermic species, which could improve organ transplantation and space flight [41][42][43][44] . Application of matrix factorization and transfer learning could determine how closely induced torpid states match naturally occurring torpor.…”

Pediatric Hypothermia: An Ambiguous Issue

“…Recently, new interest from space agencies has been expressed in “artificial hibernation”, which—if a torpor-like endogenous metabolic reduction with subsequent decrease in body temperature was somehow transferable to humans—could represent a veritable paradigm shift in organ preservation [ 97 , 98 ]. In view of the fact that spontaneous metabolic reduction in neonates and increased hypothermia tolerance in infants and children bear some similarities to natural torpor, this is an area of research that should not be dismissed a priori as mere “science fiction” [ 99 , 100 ] and may someday replace the current therapeutic approach of metabolic suppression enforced by external cooling.…”