Hibernating Squirrels Inspire New Method Of Donor Organ Preservation

Researchers are trying to unlock the secrets of hibernation in order to increase the viability of transplant organs.

Every year, around 28,000 organ transplants are performed in hospitals all over the United States. In addition, another 120,000 people are placed on waiting lists for donor organs, shows the U.S. Department of Health and Human Services.

Given that only 40 percent of Americans are registered as organ donors, the U.S. is currently facing an organ donor shortage, Gizmodo reports. Even when transplant organs are available, they still have a short expiration date and need to be quickly delivered to the recipients.

For instance, donor kidneys have a shelf life of a maximum 30 hours and have to be used within that short timeframe or they start to deteriorate. At the same time, other organs, such as the heart, the lungs, and the liver, have an even shorter viability window.

This poses a substantial problem for people on transplant lists that can’t receive the organs in time. This is why researchers are constantly looking for new and viable methods to preserve donor organs.

A creative solution may have come forth after scientists observed the process through which hibernating animals are able to lower their core body temperature to just above freezing, LiveScience reports.

In a study published this week in the journal Cell, researchers at the National Eye Institute (NEI) in Maryland, a part of the National Institutes of Health (NIH), explore the cellular mechanisms that help thirteen-lined ground squirrels make it through hibernation, in hopes of adapting them to increase the viability of transplant organs.

“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,” study co-author Wei Li said in an NIH news release.

Li, who is a senior investigator in the NEI Retinal Neurophysiology Section, argues that the long-term preservation of donor organs could be greatly improved by unlocking the secrets of hibernation. His team studied the brain cells of thirteen-lined ground squirrels (Ictidomys tridecemlineatus), small hibernating rodents common to central North America, and reached a very surprising conclusion.

During hibernation, these animals are able to get their body temperature down to nearly 32 degrees Fahrenheit (or zero degrees Celsius) while also dropping their heart rate to 10 times slower than their usual 200 beats per minute. The researchers uncovered that these hibernating squirrels can pull off such an impressive feat due to the unique structure of their cells.

Mammalian cells are made up of structural networks lined with small tubes called microtubule cytoskeletons, which help transport molecular compounds that are needed for cellular health and survival. However, these microtubule cytoskeletons, which are particularly vulnerable to cold, respond differently to near-freezing temperatures in the case of thirteen-lined ground squirrels.

The paper compared the squirrels’ neural cells with other mammalian brain cells from human and rats and discovered that the microtubule cytoskeletons kept the hibernating squirrels’ cells from dying when exposed to cold temperature. This didn’t occur in the human and rat brain cells, in which the microtubule cytoskeletons collapsed under the effects of the cold, resulting in cellular death.

“Hibernation in a dish”

To better understand the process, Li’s team replicated it in the lab, calling it “hibernation in a dish.” The researchers reprogrammed cells of newborn ground squirrels into stem cells, which later developed into various types of squirrel cells — all under the team’s microscope, from where they could observe how each type of cells adapts to the cold.

The NEI team uncovered that one reason for the microtubule cytoskeletons’ resilience to low temperatures was related to the mitochondria, also known as the cellular “powerhouses.”

The experiment revealed that, when exposed to cold temperatures, the mitochondria in human cells excessively secrete a byproduct of metabolism called reactive oxygen species (ROS), which makes the microtubules collapse. By comparison, the mitochondria of hibernating squirrels maintain low ROS levels.

After making this discovery, the researchers tested a combination of inhibiting drugs on human and rat cells to try and curb the production of ROS and obstruct protease activity. The results showed that the drug combination preserved the microtubule structure in cells from non-hibernating mammals.

“In addition to the implications for organ transplantation, these findings pave the way for future studies looking at possible therapeutic applications. For example, inducing hypothermia is a commonly used strategy to protect the brain following a traumatic injury, but the potential benefits are weighed against the potential harm from cold-induced cellular damage,” notes the NIH news release.

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