Stem cell strategies for the treatment of chronic asthma
Research type
Research Study
Full title
Exploring the role of stem cell strategies for the treatment of chronic asthma
IRAS ID
184867
Contact name
Mohammed Haris
Contact email
Sponsor organisation
University Hospitals of North Midlands NHS Trust
Duration of Study in the UK
1 years, 6 months, 0 days
Research summary
Research Summary:
Chronic asthma is often accompanied by changes to the structure of the airways resulting in thickening of the airway wall with stiffened fibrotic tissue, reducing the available airway volume. This reduced volume coupled with the contraction of the airway smooth muscle cells results in the tightening and wheezing during an asthma attack. Asthma itself is often triggered by an exaggerated response of the immune system to an external allergen. Repeated events can result in altered and partially irreversible airway remodelling, increasing the likelihood of increased attack severity.
Stem cells, particularly those derived from bone marrow, may have important roles to play in the management of chronic asthma. These roles are due to the ability of stem cells to produce a variety of molecules which can both reduce immune responses to allergens, and which may reverse the airway structural damage. We would like to see the effect of stem cells (commercially available) on the cells from asthmatic patients compared to non-asthmatic participant cells.
We plan to compare the effects of stem cell conditioned media, containing secreted molecules, on the responses of airway cells from 3 groups of participants:
Group 1: Non-asthmatics
Group 2: Mild/moderate asthmatics
Group 3: Severe asthmatics
Participants will be recruited from the Royal Stoke University Hospital; cells will be obtained from via bronchoscopy with bronchoalveloar lavage, brushing and biopsy. Cells will then expanded using in vitro cell culture techniques to obtain sufficient numbers for experimentation. These expanded cells will be incorporated into collagen gels and their behaviour when exposed to insults that are known to provoke an asthmatic phenotype (IgE and type two cytokines) will be assessed. The ability of bone marrow mesenchymal stem cell conditioned media to change this response will be determined.Summary of Results:
The aim of this laboratory study was to better understand whether products released by adult bone marrow stem cells could reduce inflammation and help to repair or prevent changes in the lining of the airways in people with asthma.
To do this, we planned to create laboratory models using samples donated by participants with asthma and allergy, including airway brushings, small biopsies, and fluid samples collected during bronchoscopy. We also obtained stem cells from commercial bone marrow sources to prepare materials for testing in these models.
Unfortunately, the study was not completed as originally planned. Progress was affected by staffing and administrative challenges, as well as disruption caused by the COVID-19 pandemic. Because of this, the final stage of testing whether stem cell products improved the asthma models could not be fully carried out.
However, much of the groundwork for the study was successfully completed using the small number of collected samples. These samples collected from participants allowed us to grow cells from the airway lining in the laboratory. These cells could be stored, providing a valuable resource for future research. We were also able to develop methods to encourage these cells to mature into specialised airway cells, including mucus-producing cells and cells with cilia (tiny hair-like structures that help clear the airways).
Finally, we also developed methods to grow fibroblasts from the samples, another important cell type involved in asthma attacks, as well as airway repair and scarring, although these were initially more difficult to isolate.
As planned, the bone marrow stem cells were successfully prepared and their culture products collected for future experiments.
Although the full planned study could not be completed, the participant samples enabled the creation of important laboratory tools and methods that will support future asthma research into airway inflammation and repair.
We are grateful to all participants who contributed samples to this research.REC name
Wales REC 6
REC reference
16/WA/0022
Date of REC Opinion
1 Mar 2016
REC opinion
Further Information Favourable Opinion