Jellyfish, salamanders, corals, fish, and insects all share a remarkable ability: they can regrow parts of their bodies. They reconstruct bones, muscles, skin, blood vessels, and nerves with such precision that the missing section seems to vanish as if it never left. Recent work has shown that functional tissue regeneration hinges on the formation of a blastema, a tumor-like mass of undifferentiated cells that forms at the injury site. This blastema not only repairs damage but also guides the re-creation of the missing extension.
A pinkish, fingernail-sized jellyfish called Cladonema can regenerate a tentacle in just two or three days. How the blastema forms in this species remains a mystery.
A team in Japan reported that cells proliferating in a way similar to stem cells appear at the injury site. These cells, actively growing but not yet specialized, contribute to the blastema and help shape the new tissue.
The researchers published their findings in Plos Biology. The authors note that these proliferative cells are not typical stem cells but residents of the tentacle that participate in regeneration. The study’s author Yuichiro Nakajima of the University of Tokyo explains that repair-specific proliferative cells mainly contribute to the epithelial layer of the newly formed tentacle.
In Nakajima’s view, resident stem cells located in and near the tentacle create entire cell lineages during both normal maintenance and regeneration. They sustain the cells required throughout the animal’s life, while the repair-specific proliferative cells appear only when an injury occurs.
resident stem cells
Unity strengthens recovery. Resident stem cells paired with repair-specific proliferative cells enable rapid tentacle regeneration within a few days, Nakajima notes.
The study also highlights how blastema formation differs among animal groups, with lead author Sosuke Fujita of the University of Tokyo contributing to the broader picture of the mechanism.
The aim was to understand blastema formation using the tentacle of the cnidarian jellyfish Cladonema as a regenerative model in non-bilateral animals, those that do not develop with a clear left-right symmetry during embryogenesis. This contrasts with bilateral animals, where mechanisms for blastema formation are better understood.
In salamanders, which are bilateral, limbs can regenerate because stem cells are oriented to specific cell lineages. This process shares similarities with the repair-specific proliferative cells observed in jellyfish.
Again, the cellular origins of the repair-specific proliferative cells seen in blastema remain unclear. Researchers note that current tools are too limited to map the origins of these cells or to identify distinct stem cell populations.
As Nakajima puts it, it would be valuable to introduce genetic tools to track cell lineages and manipulation in Cladonema. Ultimately, understanding blastema formation in regenerative animals, including jellyfish, may reveal cellular and molecular components that could enhance human regenerative abilities.
a natural process
Could humans steer regeneration to grow new appendages? Cell renewal via stem cells is a natural process. It is evident in hair and nail growth and in the healing processes that mend skin and other tissues.
Organ regeneration in humans remains limited. Mammals can restore some liver and pancreas tissue and repair skeletal muscle and peripheral nerves, but not on the scale seen in amphibians and certain fish. An Argentinian cardiologist, Hernán C. Doval, notes that regeneration in some cases can extend beyond limbs to areas such as the lens, retina, and heart muscle, though this is not typical for humans.
During limb regeneration, Doval emphasizes that in young children with distal finger amputations, excellent fingertip regeneration can occur if the stump skin is not sutured too tightly.
His conclusion points to a possible path: to move regenerative capacity toward humans, scientists may need to transiently and simultaneously block two tumor suppressors known as ARF and Rb. This could unlock the mechanisms that evolution already uses in lower vertebrates to adapt them to human healing. The idea is to explore differentiation control in tissues that regenerate best in other species as a stepping stone for new therapies.
Reference report: PLOS Biology, 2023. This study highlights the intriguing idea that a combination of resident stem cells and repair-specific proliferative cells drives rapid tissue restoration in jellyfish. Ethical and safety considerations will guide any future work in translating these insights to human medicine.