Cystic Fibrosis Treatment Revolutionized by Mini-Organs from Children's Cells (UNSW Study)

The UNSW Breakthrough in Cystic Fibrosis Research

Researchers at the University of New South Wales (UNSW) Sydney have made a significant advance in treating cystic fibrosis (CF), a life-limiting genetic disorder affecting thousands of Australians. By growing tiny 'mini-me' organs, known as organoids, from children's own cells, scientists can now test which treatments work best for individual patients. This personalized approach promises to transform care, moving beyond one-size-fits-all therapies to precision medicine tailored to each child's unique biology.

Cystic fibrosis impacts the respiratory, digestive, and other systems due to faulty proteins that cause thick mucus buildup. In Australia, around 3,800 people live with CF, and tragically, two individuals die every four weeks from complications like chronic lung infections. The UNSW team's work focuses on children aged 5 to 17, using nasal cells to create lung organoids that mimic the patient's actual tissue response to drugs.

Understanding Cystic Fibrosis and Its Challenges

Cystic fibrosis, often abbreviated as CF, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This gene codes for a protein that functions like a gate on the surface of epithelial cells lining the lungs, gut, pancreas, and other organs. Normally, the CFTR gate opens to allow chloride ions and water to flow out, keeping mucus thin and hydrated to trap and clear bacteria.

In CF patients, over 2,000 known mutations disrupt this process—the gate might stick closed, mislocate, or degrade prematurely. This leads to sticky mucus that clogs airways, fosters infections, and causes inflammation and organ damage. Even patients with the same mutation show varied responses; studies indicate only about 40% improve on a given therapy, while others see no benefit or even decline.

Traditional treatments include mucus-thinning drugs, antibiotics, and nutritional support, but the game-changer has been CFTR modulator drugs like Trikafta (elexacaftor/tezacaftor/ivacaftor). Approved in Australia since 2021, these target specific mutations and are now accessible to over 90% of CF patients via the Pharmaceutical Benefits Scheme (PBS). Yet, predicting individual responses remains tricky, highlighting the need for tools like organoids.

What Are Patient-Derived Organoids?

Organoids are three-dimensional, miniature replicas of organs grown in the lab from a patient's stem cells. Unlike flat cell cultures or animal models, organoids self-organize into structures that closely replicate the architecture, function, and genetics of real organs. For CF research, intestinal or airway organoids are particularly valuable because they express functional CFTR proteins that respond to drugs just like in vivo.

The process begins with a simple, non-invasive biopsy—such as rectal cells for gut organoids or nasal brushings for lung organoids. These contain adult stem cells that are isolated, expanded, and cultured in a nutrient-rich gel matrix. Over weeks, they bud into crypt-like structures with lumens (central cavities) where fluid dynamics can be measured. A key assay is the forskolin-induced swelling (FIS) test: adding a modulator drug causes responsive organoids to swell as CFTR restores ion and water transport, providing a quantifiable readout of efficacy.

How UNSW Creates and Tests Mini-Organs Step-by-Step

UNSW's Molecular and Integrative Cystic Fibrosis Research Centre (miCF_RC) leads in paediatric organoid theratyping. Here's the step-by-step method:

• Sample Collection: Nasal epithelial cells are gently brushed from the child's nose during a routine clinic visit.
• Stem Cell Isolation: Cells are dissociated and stem cells selected using specialized media.
• Culture Expansion: Stem cells form organoids in Matrigel domes with growth factors like EGF, Noggin, and R-spondin.
• Drug Testing: Mature organoids (2-4 weeks old) are stimulated with forskolin ± modulators; imaging tracks swelling over hours.
• Analysis: Response quantified as area increase; 'dancing organoids' indicate strong positive results.

This human-specific model bypasses species differences in animal testing, offering predictive power for clinical outcomes.

Details of the Landmark Paediatric Study

Published in Thorax (DOI: 10.1136/thorax-2025-223153), the study involved 24 Australian children with common CFTR mutations. Researchers tested organoids against all four clinically available modulators, tracking responses alongside real-world metrics like forced expiratory volume (FEV1) lung function and sweat chloride levels during therapy switches.

Prior UNSW work guided treatments for ultra-rare mutations ineligible for trials, but this was the first head-to-head paediatric comparison. Collaborators included The Australian National University and University of Melbourne, funded by NHMRC grants.

Lead author Laura Katherine Fawcett presented early data at TSANZ 2023 and ECFS 2023 conferences.

Key Findings: Organoids Outperform Genetics

Organoid swelling precisely mirrored clinical improvements—children whose organoids 'danced' saw lung function gains and reduced sweat chloride. Crucially, whole-genome sequencing added no predictive value beyond known mutations, underscoring organoids' superiority for heterogeneous responses.

For instance, among same-mutation groups, organoids identified the 40% responders and flagged non-responders, preventing futile trials of costly drugs (Trikafta costs ~$200,000/year untreated). This could save months of ineffective therapy, reducing side effects and hospitalization risks.

• Strong correlation: Lab response → clinical success in 80-90% cases.
• Personalization: Matched optimal modulator per patient.
• Paediatric first: Validated for kids, where data is scarce.

Meet the Researchers Driving Change at UNSW

Associate Professor Shafagh Waters, Scientia Fellow and 'organoid queen,' heads the effort. With expertise in stem cell biology for paediatric lung/gut diseases, she explains CF simply: "Picture an airport gate stuck closed—organoids let us test which key unlocks it." Her NHMRC-funded program spans 32 grants.

Professor Adam Jaffe, respiratory paediatrician, pushes for clinical rollout: "This needs to be a standard pathology test, requestable by any doctor." Their work positions UNSW as a hub for rare disease innovation. Aspiring researchers can find opportunities via higher ed research jobs in Australia.

Implications for Australian CF Patients

Australia's ~3,800 CF patients, especially the heterogeneous paediatric group, stand to benefit immensely. Currently, no formal pathway exists for organoid-based modulator access, unlike some countries. Reforms in health technology assessments could change this, standardizing tests to optimize PBS-subsidized therapies.

Benefits include fewer exacerbations, better quality of life, and cost savings for the system. For families, it means hope: one child with a rare mutation accessed life-changing drugs via organoid proof.Read the full UNSW announcement.

Global Context: Countries Leading with Organoids

The Netherlands pioneered intestinal organoids for CF theratyping, with biobanks guiding 90% of patients to optimal drugs. The US and Europe follow, approving modulators based on organoid data for trial-ineligible cases. Australia's smaller, diverse population makes UNSW's airway organoids especially relevant.Explore NSW medical research advances.

Future Directions and Challenges Ahead

Next steps: Validate scalability, accredit labs, and integrate into clinics. Challenges include standardization, cost (~$5,000/test initially), and ethical biopsy consent. UNSW aims for routine use within years, expanding to other rare diseases.SciMex coverage.

• Scale production for national network.
• Combine with AI for faster analysis.
• Extend to adult CF and multi-organoids.

Broader Impact on Precision Medicine and Research Careers

CF serves as a monogenic model for complex diseases, accelerating organoid use in cancer, IBD, and beyond. UNSW's success highlights Australia's research prowess, attracting talent amid global demand for stem cell experts.

For academics eyeing research assistant roles or postdoc positions, fields like organoid tech offer exciting paths. Check Australian university jobs or university jobs for openings. Share your experiences on Rate My Professor.

Conclusion: A New Era for CF Care Down Under

UNSW's mini-organs herald personalized CF treatment in Australia, blending cutting-edge research with patient hope. As therapies evolve, platforms like higher ed jobs and career advice support the next generation. Stay informed and explore opportunities today.