From the revived corpse of Frankenstein’s monster to the disembodied hand, “Thing,” in the Addams Family, reanimated tissue is one of the most enduring images in science fiction. The discovery of a sea floor-dwelling sea cucumber that scientists are calling a “real-life zombie” suggests that there may be some basis for that image in nature.
Scientists headed by a team at Memorial University of Newfoundland showed the continued viability of amputated tissue from the sea cucumber Psolus fabricii for more than three years in natural seawater. It’s the first known report of the long-term survival—and continued growth—of discarded tissue outside of a highly controlled, sterilized environment.
The discovery that these living P. fabricii explants (LiPfe) can survive for years in natural seawater without any supplementation challenges assumptions of what’s possible for tissue immortality and could have implications in areas including regenerative biology and tissue engineering. The findings could also lead to the development of experimental models for biological research that are more widely accessible, without the ethical and logistical challenges associated with many existing cell lines.
“We haven’t grown a new, complete sea cucumber yet, but we are seeing pretty stunning growth and diversification of cells literally years after this tissue was removed,” said research lead Rachel Sipler, PhD, a Bigelow Laboratory for Ocean Sciences senior research scientist. “It’s like a lizard that loses its tail. We know some lizards can grow new tails; we’re talking about whether the tail can grow a new lizard.”
Reporting on their findings in Science Advances (“Natural tissue immortality: Indefinite survival of sea cucumber explants,”) Sipler and colleagues stated, “Our findings challenge conventional perceptions of tissue immortality and present a new class of experimental model, free from ethical concerns, with substantial implications for regenerative biology, biomedical research, and tissue engineering.”
Over the last 200 years, scientists have tried to achieve cellular and tissular survival outside living hosts, “… but efforts have been met with limited success due to the highly degradable nature of tissue itself,” the authors wrote. Since the mid-20th century, scientists have made significant breakthroughs with immortal cell lines, such as HeLa cells, that can be grown in a lab and proliferate indefinitely for long-term research. In earlier studies, tissue cultures have only been maintained under axenic conditions that are tightly controlled, rigorously maintained, and lack any bacteria or other organisms. Even then, they have not demonstrated signs of actual healing and growth, nor retained the ability to move independently. “While immortal cell lines demonstrate indefinite proliferation in vitro, they lack structural integrity and complex tissue interactions,” the team continued. “Achieving this with complex, structured tissue represents the next step.”
Many echinoderms, including sea cucumbers, are known to display impressive regeneration capacity and negligible cell aging. “In the ongoing effort to understand tissue culture, regeneration, and immortality, researchers have naturally been drawn to echinoderms, a phylum with genetic and evolutionary links to vertebrates and examples of both extreme regenerative capacity and negligible cellular senescence,” the investigators noted. Lost tissue, though, was always assumed to eventually decay or die.
Yet, in what Sipler calls a product of “keen observation,” the researchers noticed that some discarded tissue from a tube foot of a sea cucumber hadn’t decayed after a number of weeks. In fact, it seemed to be growing. The researchers then ran a number of experiments in flowing seawater with tissue removed from the feet, main body, and tentacles of three individuals of P. fabricii, a cold-water species of sea cucumber.
They found evidence of diversifying cells, immune activity, and tissue reorganization in the explanted tissue. “In experimental trials, these explants, termed LiPfe (living immortal P. fabricii explants), displayed immune activity, cell cycling, tissue reorganization, and absorption of dissolved amino acids, underscoring their active living state,” they noted. And in the absence of a mouth, the cells appeared to be getting nutrients by absorbing amino acids dissolved in the seawater.
Even after three years, when the researchers stopped the experiments in order to publish, the tissue was still active. This ability to survive in a complex, stressful environment, Sipler said, makes this cell line unique compared to other tissue cultures. “Compared to other cells or tissues grown under laboratory setups that required strict parameters, including axenic conditions, LiPfe required nothing apart from natural running seawater,” they wrote. “Comparative experiments conducted on explanted tissues from related species demonstrated no equivalent tissue survival, highlighting the unique properties of P. fabricii, which do not have parallels in the current literature.”
“Natural seawater is just about the most microbially diverse, least clean approach we could take experimentally,” Sipler added. “Yet, that rich environment full of bacteria and all this organic matter was actually feeding them and allowing this tissue to heal and grow.”
The implications for biomedical sciences and engineering, the authors said, are profound, with potential applications in everything from tissue regrowth to anti-microbial healing. In their paper, the authors stated, “The discovery of LiPfe challenges the boundary between organismal life and cellular autonomy, compelling a redefinition of what it means for tissue to be alive.”
The discovery opens up new opportunities for biological research and education more broadly. The tissue they’ve preserved not only shows an unprecedented ability to maintain its structural integrity and complexity in culture. It can also be grown more easily in the lab and, as an invertebrate, isn’t subject to as many research restrictions, making it useful in contexts where there are legal obstacles or limited biosafety infrastructure for using human-based or other vertebrate cell lines.
As an oceanographer, Sipler noted that the exciting discovery drives home the incredible untapped potential of ocean life. “The best advances in science are made when you find a natural analog for what you’re studying,” she said. “Here is this species that has this groundbreaking ability, and we had no idea. It’s a reminder of how much is yet to be discovered in the marine environment, and how important it is to protect these resources that may hold really valuable knowledge for us.”
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