New Insights / What If the Secret to Repairing Human Lungs Is Already Written in Nature?

What if the key to regenerating human lungs lies in understanding how nature already rebuilds them?

A new study led by Arzu Güneş, Duygu Gürsoy Gürgen, Arife Ahsen Kaplan, İlkay Özdemir and İlknur Keskin at Istanbul Medipol University SABITA reveals how the axolotl lung undergoes a remarkable structural transformation during the transition from aquatic to terrestrial life—offering new insights into the biological basis of lung regeneration.

Using histological, immunohistochemical and ultrastructural analyses, the researchers compared neotenic (aquatic) and metamorphic (terrestrial-adapted) axolotls. They found that metamorphosis triggers a coordinated reorganization of lung architecture: air spaces expand, collagen-rich tissue shifts toward elastic fibre dominance, and the blood–air barrier becomes thinner, supporting aerial respiration.

At the cellular level, the study highlights an important distinction from mammalian systems. Rather than forming strictly defined cell types, axolotl lung cells exhibit hybrid and flexible characteristics, retaining features linked to both structure and function. This suggests a non-terminal differentiation state, a feature often associated with regenerative potential.

The persistence of lipofibroblast-like (ILF-like) cells in both stages adds another layer of significance. These cells are associated with lipid metabolism, surfactant support, and potential progenitor functions, pointing to a microenvironment that may support tissue repair and reorganization.

Together, these findings provide a morphological framework for pulmonary plasticity, offering structural insights into how axolotl lungs adapt—and potentially regenerate—at the tissue level.

By revealing how structural remodeling, cellular flexibility, and microenvironmental factors interact, this work offers a new perspective on why regeneration is limited in human lungs—and how it might one day be enhanced.