From Star Wars to the Captain America franchise and beyond, the film world is filled with futuristic movies where characters are placed in a state of cold-induced suspended animation—only to be revived at a later point without suffering any long-term damage.
This phenomenon can also be seen in nature. The wood frog, a small frog common in North America, secretes an antifreeze-like substance during the winter that protects its cells from freezing while it goes into a state of suspended animation. When the weather warms, the frog resumes its normal activity.
Researchers have been working for decades to find ways to replicate this process in the lab. While there have been some successes along the way—it is now possible to freeze human eggs, sperm and embryos for future in vitro fertilization, for example—several key barriers remain.
The biggest of these barriers are the damage to cells, tissues and organs caused by the formation of ice crystals during cooling and reheating process, and the toxicity of cryopreservation agents—chemicals used to preserve living material at ultra-low temperatures.
If these barriers can be overcome on a larger scale, the implications for human health will be huge—from increasing the viability of transplanted organs, to reducing the cost and logistical challenges of cell-based therapies for cancer, to solving global health challenges and creating a sustainable food supply.
Researchers from the Center for Engineering in Medicine & Surgery at Massachusetts General Hospital and the University of Minnesota’s Institute for Engineering in Medicine recently received a $26M grant from the National Science Foundation to establish an engineering research center that will develop new technologiesto get us closer to this goal.
The new center, called Advanced Technologies for Preservation of Biological Systems (ATP-Bio), also includes the University of California, Riverside, and the University of California, Berkeley, as core collaborators.
“We’ve been working on the field of low temperature biology for cryopreservation, cryobiology for almost 40 years,” says Mehmet Toner, PhD, who will be leading research efforts at Mass General along with Korkut Uygun, PhD. “It’s a greatly ignored field and it’s very complex.”
Overcoming a Major Bottleneck
The inability to preserve and restore living materials without damage has been cited as a major bottleneck in the areas of human health, biodiversity and food supply, says Toner.
“When you put things into suspended animation, you need to take energy out of the system—lowering the temperature reduces the energy and metabolism,” he says. “But the problem is—how do you bring it there without killing it and how do you bring it back again?”
ATP-Bio will have three main research thrusts aimed at finding solutions to these challenges:
1. Biological Engineering
This area will tackle problems at the pre-cooling stage, which includes developing new cryopreservation agents (CPAs) and biosystems to prepare living material for subzero preservation and return to normal function.
It this area where insights from wood frogs and other freeze-tolerant organisms could play a crucial role.
2. Multi-Scale Thermodynamics of Water
Research here will focus on preventing or limiting the damage caused by ice crystallization during the cooling process through the strategic use of CPAs and manipulating cooling conditions.
3. Rapid and Uniform Warming
Efforts here will focus on limiting the damage caused by ice crystal formation as cryopreserved specimens are warmed from subzero temperatures.
Potential Applications of Biopreservation
In the short-term, advances in biopreservation could reduce the cost and logistical challenges of cell therapies such as CAR-T cells for cancer, increase the number of viable donor organs, enable the preservation and transportation of lab models for drug development, and accelerate research into global health challenges such as malaria.
“If we could put living things—from organisms, organs, tissues, cells to small bugs and bacteria—into suspended animation so we can store and ship them, it enables all kinds of applications,” Toner explains.
More ambitious long-term goals include stockpiling tissues and blood vessels to be used for trauma care in mass casualty events and preserving fish embryos for global food sustainably.
The center will also explore strategies for whole-body cryopreservation that could be used on the battlefield or for astronauts undergoing long-term space travel.
Building Supply Chains and Distribution Networks
In addition to developing the technologies themselves, researchers at the center will play a leading role in building supply chains and ensuring equal distribution of biopreserved materials.
“That’s why I call it the Amazon of living things,” Toner says. “It’s the management and shipment and storage of living things so we can get them to people around the world when they need it.”
“It’s far more complicated than sending sneakers or books around the world, of course, but that’s what is needed to move the field of healthcare forward.”
Research at Mass General Brigham
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