There is no architect, scientist, nor inventor on Earth that has designed as much as Mother Nature. She has twirled shells into fractal perfection, twisted DNA into infinite forms, and blasted boom-claps of thunder across pitch-black skies.
Now, another tiny design of hers could spur scientists to devise a way to preserve human organs for transplantation – and the key to unlocking that secret may be found in a humble ground squirrel.
For the study, published in the journal Cell, the team from the NIH National Eye Institute explored the ability of 13-lined ground squirrels (Ictidomys tridecemlineatus) to survive the harsh chill of winter. This “remarkable feat of cellular preservation” is non-existent in humans and the biological factors behind the squirrels’ hibernation feats remain fuzzy.
The importance of such work is clear in the figures: In the US alone, more than 115,000 people need a lifesaving organ transplant, with around 75,000 on the waiting list. Each day, 20 die in that wait. The need to preserve organs longer is just one crucial component in reducing these deaths.
“Kidneys, for example, are typically stored for no more than 30 hours,” Wei Li, a senior investigator in the NEI Retinal Neurophysiology Section, said in a statement. “After that, the tissue starts to deteriorate, impairing the organ’s ability to function properly after it's been rewarmed and reperfused. Heart, lungs and livers have an even shorter shelf life.”
To explore the squirrels’ unique abilities in a controlled setting, the researchers created “hibernation in a dish”. Essentially, they reprogrammed cells taken from newborn squirrels to become induced pluripotent stem cells (iPSCs) that can become any cell in the body.
In this instance, they wanted the cells to retain the cold-adaptive characteristics of the adult squirrel cells. They then compared the expression of human and squirrel cell-derived neurons. They found differences in the reaction of mitochondria, which are responsible for providing energy to the cell in the form of adenosine triphosphate (ATP).
In human neurons, the cold triggered mitochondrial stress, resulting in the overproduction of reactive oxygen species – a byproduct of metabolism – and contributing to microtubule destruction.
Notably, human neurons also had trouble with lysosomes, an organelle that helps dispose of waste inside the cell. The cold exposure caused them to leak enzymes that digested nearby microtubules.
To switch a not-so-good situation to a better one, the researchers tried to make human cells more like the hibernating ones found in squirrels. To do this, they used two drugs: one to inhibit the production of ATP and the second to inhibit the unwanted enzyme activity. The combination of both drugs preserved the microtubule structure from destruction.
While more work needs to be done, such a finding could one day lead to improved techniques to preserve organs and even to possibly induce hypothermia in patients with traumatic brain injuries, although we're not there yet.
“By understanding the biology of cold adaptation in hibernation, we may be able to improve and broaden the applications of induced hypothermia in the future, and perhaps prolong the viability of organs prior to transplantation,” Li said.
It seems we still have much to learn from Mother Nature’s molecular tricks – even in the form of a humble sleeping squirrel.