Tissue Engineering Approaches to Treat COPD

  • End date
    Dec 31, 2023
  • participants needed
  • sponsor
    University Hospitals of North Midlands NHS Trust
Updated on 15 May 2021


The study is a pilot/laboratory study comparing lung tissue from control participants with tissue from COPD participants with a chronic bronchitis or emphysema phenotypes. Tissue will be characterised mechanically and biochemically.

Lung cells, including DASCp63/Krt5 with a possible role in disease pathology, will be isolated, expanded in vitro, characterised, and banked. Biomaterials will be selected and tested with regards to mechanical and physical properties and selected for use in the production of TELEs with properties matched to healthy and diseased lung tissue.

The resulting TELEs will be tested in an ex vivo tissue culture model to determine the extent of their integration with lung.


Chronic obstructive pulmonary disease (COPD) is currently ranked as the third leading cause of death with an annual associated global healthcare cost of 1.3 trillion (1). It is the second most common cause of emergency hospital admissions with high morbidity and mortality. COPD results in a progressive loss of lung function, leading to respiratory failure. This loss of lung function is associated with repetitive cycles of inflammation and parenchymal scarring leading to the development of emphysema. This is a consequence of the breakdown of the delicate parenchymal structures and lung remodelling, with accumulation of fibrous tissue and loss of the alveolar-capillary functional units that are essential for effective gas exchange. Macroscopically the lungs become stiffer and unable to support the patient through the physiological inhalation/exhalation breathing cycles (2).

The presence of emphysema also results in the loss of lung elastic recoil as pockets of air form in place of damaged bronchioles and alveoli reducing the available volume for the next inhalation. The collapse of the airways during exhalation leads to increased lung volumes causing hyperinflation and gas trapping. Patients become progressively symptomatic with increasing breathlessness, reduced exercise tolerance and poor quality of life.

The pharmacological treatment options for emphysema are limited; current therapy aims to improve airflow limitation, reduce airway inflammation and reduce exacerbations, but does not reverse lung damage (3). Lung transplantation and lung volume reduction surgery (LVRS) is available for a selected minority of patients with severe emphysema. The recent introduction of non-invasive endoscopic mechanical treatment with Valves reduces severely damaged lung volume and re-directs air to the healthier tissue while Coils improves elastic lung recoil (4, 5). These interventions however do not improve survival.

Previous work performed within our laboratories has determined that hydrogel/elastin-based constructs can achieve mechanical values consistent with those of the alveolar wall when seeded with lung fibroblasts (1). This raises the intriguing question of whether tissue-engineered constructs (TEC) could be used to restore mechanical integrity of the emphysematous lung, via air pocket displacement and local integration, and ultimately by regeneration of local lung architecture.

Coupled to the work described above a recent observation went some way to detailing the mechanism behind the previously misunderstood, but physiologically critical, capacity for lung tissue to regenerate following on from acute disease such as pneumonia or acute respiratory distress syndrome (6). The key appears to lie with a population of distal airway stem cells who co-express Trp63 (p63) and Keratin 5 (Krt5). These DASCp63/Krt5 cells appear to migrate to sites of injury in the lung where they have demonstrated differentiation capacity including lineages such as type I and II pneumocytes and bronchiolar secretory cells. It is crucial to our understanding of chronic lung disorders, and design of future cell-based therapies, whether these cells remain present and dormant in diseased lung tissue or lost through as yet unknown mechanisms.

Condition Pulmonary Disease, Lung Disease, Lung Neoplasm, Lung Cancer, Bronchial Neoplasm, Lung Cancer, Lung Disease, carcinoma lung, lung carcinoma
Treatment Patients undergoing standard surgery, excess tissue only will be analysed with patient consent.
Clinical Study IdentifierNCT04878445
SponsorUniversity Hospitals of North Midlands NHS Trust
Last Modified on15 May 2021


Yes No Not Sure

Inclusion Criteria

Men or women aged over 18 years-
Must be competent to give written informed consent
Scheduled to undergo clinical indicated surgery to remove lung tissue

Exclusion Criteria

Patient unable to give informed consent
Significant long term condition or lung pathology (infection, asthma, fibrotic lung diseases) other than that for which they have been referred for surgery
Post Surgery
Insufficient tissue removed to supply the laboratory study after consultation
with the Consultant histopathologist
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact



Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note