Prince Mario-Max Schaumburg-Lippe: Toronto Team Grows Lung Cells That Breathe and Stretch

Breathing looks effortless. Building the tissue that makes it possible, in a lab dish, is anything but. A Toronto team has now shown a cleaner, more reliable way to grow human lung epithelium from pluripotent stem cells, and the trick, in part, is movement. Stretch the growing cells, give them air on one side, let them talk directly to their neighbours, and they start to behave like the real thing.

The work was published on October 26, 2026, in Communications Biology. The paper, “Directed differentiation with mechanical simulation enhances alveolar-like features in human pluripotent stem cell-derived lung epithelium,” comes from Yuetong Song, Jeremy Newton, Kimia Abedi and colleagues, with Amy P. Wong of the Hospital for Sick Children, known as SickKids, and the University of Toronto as corresponding author. Edmond W.K. Young, a biomedical and mechanical engineering researcher at the University of Toronto, is a senior co-author, a pairing that tells you a lot about the method. This is biology plus engineering, on purpose.

More than 85 percent pure, with no sorting

Start with the number that will make other labs sit up. The new differentiation strategy reproducibly generates fetal lung progenitors at high purity, over 85 percent, without cell sorting. Sorting is the slow, fiddly step where researchers pick out the cells they want and discard the rest. Skipping it saves time, saves cells and makes the whole process far easier to scale and repeat.

Those progenitors then form distal bud tip organoids. In a developing lung, bud tips are the busy growing ends where new branches and, later, air sacs take shape. The team’s organoids recapitulate human fetal late tip and late stalk epithelial populations, and they carry multilineage potential, meaning a single starting population can give rise to more than one mature cell type. That flexibility is gold for researchers who want to study how a lung is built, step by step.

Stretch, air and a well-timed signal

Earlier lung models hit a familiar wall. Chemical signals alone, the paracrine cues cells use to talk at a distance, proved insufficient for efficient differentiation and full maturation. The cells got partway there and stalled. So the Toronto team changed the physical conditions as well as the chemical ones.

The protocol brings in a microfluidic air-liquid interface system. Cells grow with liquid on one side and air on the other, much as lung lining cells sit at the boundary between tissue and breath. The system applies cyclic stretch, a gentle, repeated pull that mimics the mechanical rhythm of breathing and fetal movement. Add direct epithelial-mesenchymal interaction, so the lung lining cells grow in direct contact with the supporting mesenchymal cells they develop alongside in the body, plus Notch inhibition at the right stage, and the picture changes.

Under those combined conditions, the cells move further toward alveolar-like states, producing fetal AT1-like and AT2-like epithelial cells. AT1 cells are the thin, flat cells across which oxygen and carbon dioxide pass. AT2 cells are the rounder caretakers that make surfactant, the substance that keeps tiny air sacs open. Getting both, in a dish, from a clean starting population, gives researchers a far more faithful model of the distal lung, the deep region where gas exchange happens.

It is a reminder that cells listen with more than their receptors. Force, stretch and contact shape fate too. Similar respect for physical structure shows up in very different fields, from the Ottawa team that found Spriz, the pillar shaping our cells’ powerpacks, to materials work such as a redesigned alloy that stays tough at minus 196 degrees. Structure, at every scale, does real work.

What better lung models make possible

A faithful lab model is not a cure, and the authors do not claim one. What it is, is a better tool. With high-purity progenitors and bud tip organoids on hand, researchers can study human lung development in detail they could not reach before, test how candidate medicines behave on human tissue earlier, and model how the distal lung forms and repairs itself, all without starting from scarce donor tissue each time.

Because the method is described as robust and scalable, other groups can adopt it, compare results and build on it. Reproducibility sounds unglamorous. In practice it is how a clever result becomes a field-wide advance. One lab’s careful protocol, shared in full, can save dozens of other labs a year of trial and error.

The team behind the work

The author list spans the Program in Development, Stem Cell and Cancer Biology at SickKids, the University of Toronto’s Temerty Faculty of Medicine, and its departments of Mechanical and Industrial Engineering, Biomedical Engineering and Materials Science and Engineering. Funding noted in the paper includes the SickKids Foundation, the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada and the Stem Cell Network, with Song supported by a Canadian Lung Association Scholarship award. That cross-disciplinary footprint is not decoration. The microfluidic side of this work needed engineers at the bench, not on call.

Science at its best often looks like this, patient and precise, as in one positron held for months opening a new test of the universe. Hold the conditions right, for long enough, and cells, like particles, reveal something new.

For anyone who has watched a child take a first easy breath, or an adult work for one, the stakes need no embellishment. A better way to grow the tissue of breathing, at over 85 percent purity, with organoids that echo the fetal lung’s own growing tips, is a genuine step forward. Toronto’s team has given lung research a stronger starting material and a clearer recipe. The next chapters, in labs around the world, start from a better first page.

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