Jellyfish regenerate their limbs in days, can humans do the same?

Numerous species, including jellyfish, salamanders, corals, fish, and insects, possess the remarkable ability to regenerate body parts. They can rebuild bones, muscles, skin, blood vessels, and nerves so precisely that it’s hard to believe the part was ever missing.

A few years ago, it was discovered that the key to this regeneration lies in the formation of a blastema, a cluster of undifferentiated cells akin to a tumor, at the site of the injury. These blastemas repair the damage and grow into the missing appendage.

Take, for example, a species of jellyfish the size of a pinky nail, known as Cladonema. It can regenerate a tentacle in just two to three days—however, the process of how the blastema forms remains a mystery.

Injured tissue prompts cell regeneration

Recent research from a team based in Japan has shed light on this process. They found that stem cell-like cells, which are in a state of active growth and division but have not yet differentiated into specific cell types, also appear at the injury site and contribute to the formation of the blastema.

The research team’s findings, recently published in Plos Biology, highlight some important distinctions in the cellular mechanisms of regeneration. Yuichiro Nakajima, a member of the team from the University of Tokyo, points out that the proliferative cells involved in forming the blastema are not the same as the resident stem cells found in the tentacle.

Nakajima explains that these repair-specific proliferative cells primarily contribute to forming the epithelium, the thin outer layer of the newly regenerated tentacle.

In contrast, the resident stem cells, which are located within and near the tentacle, play a broader role. They are responsible for generating all cell lineages during both homeostasis and regeneration, essentially maintaining and repairing any cells required throughout the jellyfish’s lifespan. Interestingly, these repair-specific proliferative cells only emerge at the time of injury.

Resident stem cells

"Union creates strength. Nakajima explains, "The resident stem cells and the repair-specific proliferative cells together enable the functional tentacle to regenerate rapidly within a few days."

This finding also reveals how blastema formation differs between different groups of animals, highlights lead author Sosuke Fujita, also from the University of Tokyo.

The study aimed to explore the process of blastema formation, using the tentacle of the cnidarian jellyfish Cladonema as a model for non-bilateral animals. These are animals that do not develop bilaterally (from left to right) during embryonic development. The mechanisms of blastema formation are better understood in bilateral animals.

For instance, salamanders, which are bilateral animals, can regenerate limbs due to the presence of stem cells that are specific to certain cell types. This process seems to operate similarly to the repair-specific proliferative cells observed in jellyfish.

However, the cellular origins of these repair-specific proliferative cells in the blastema remain a mystery. The researchers note that the current tools available for investigating their origins are too limited to determine the source of these cells or identify other distinct stem cells.

Nakajima emphasizes the need for genetic tools that allow for the tracking of specific cell lineages and manipulation in Cladonema. He believes that understanding the mechanisms of blastema formation in regenerative animals, including jellyfish, could potentially help us identify cellular and molecular components that could enhance our regenerative capabilities.

A natural process

"So, could humans possibly regenerate appendages? Naturally occurring cellular regeneration through stem cells is a process evident in various processes such as hair growth, nail growth and wound healing that affects the skin or other body parts."

"Organ regeneration presents a different issue. Humans, like other mammals, can regenerate large parts of the liver and pancreas, and repair skeletal muscle and the peripheral nervous system but only to a limited extent. This stands in contrast to the ability that amphibians and fish possess to repair most of their organs, "including the lens, retina, heart muscle and central nervous system, in addition to recreating amputated limbs and fins," as Hernán C. Doval, an Argentine cardiologist, noted in one of his works.

Doval emphasizes that in the case of young children who have experienced distal amputations of their fingers, perfect regeneration of the fingertip is possible. However, this only occurs if the skin of the stump is left unsutured.

The team concluded that to harness the potent regenerative abilities of aquatic salamanders and zebrafish for human benefit, two tumour suppressors known as ARF and Rb must be temporarily and concurrently inhibited.

Doval expressed fascination at the discovery of a mechanism that evolution had previously devised and utilized in lower vertebrates and later adapted for humans. This mechanism of “dedifferentiation” could potentially aid in the development of new techniques for regenerating our damaged tissues.

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