Breathing difficulties in asthma and chronic obstructive pulmonary disease (COPD) are partly driven by abnormal smooth muscle in the airways, which either contracts too strongly or undergoes lasting structural changes. Despite this, there are currently no treatments that reverses smooth muscle remodelling in these diseases. To study these processes in detail, this project aims to generate smooth muscle cells from induced pluripotent stem cell (iPSC)-derived lung mesenchyme, providing a model to investigate disease mechanisms and explore new treatment strategies.
Impact
Asthma and chronic obstructive pulmonary disease (COPD) are among the most prevalent chronic respiratory diseases globally, affecting millions of individuals. In Australia alone, approximately 11% of the population live with asthma. Despite their widespread impact, current treatments primarily focus on managing symptoms and inflammation, with limited options targeting the underlying smooth muscle remodelling and dysfunction. This research aims to bridge that gap by developing smooth muscle cells from induced pluripotent stem cell (iPSC)-derived lung mesenchyme. Ultimately, this approach holds the potential to pave the way for more effective therapies that address the root causes of asthma and COPD, improving the quality of life for millions and reducing the associated healthcare burden.
reNEW research
Our team have optimised conditions for generating human iPSC-derived lung mesenchyme (iLM) in vitro. The differentiation process recapitulates key developmental milestones, guiding mesodermal lineage specification toward lateral plate mesoderm, followed by patterning into lung-specific mesenchymal progenitors.
Image description
iPSC-derived lung mesenchyme (iLM) were specified further to smooth muscle using defined media conditions. In this image, a green “wave” of smooth muscle cells (marked by α-SMA) cascades over surrounding immature iLM (stained red to mark PDGFRα).
Credits
Patrick Law, Research Assistant, Werder Lab, reNEW Melbourne.
