RGM.20.009 – REStoration Of LUng funcTIon lOss iN emphysema (RESOLUTION)
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. The prevalence of CODP will increase with the ageing of our population, thus having a strong impact on our society because of the high morbidity, mortality and burden on healthcare. COPD is caused by inhaled toxicants (e.g. cigarette smoke, environmental pollutants and job-related exposures) and characterized by aberrant inflammatory, injury and repair processes in the lungs. This results in chronic airway inflammation (bronchitis) and/or destruction of functional gas exchange units (emphysema), leading to progressive loss of lung function, which is irreversible, even after smoking cessation. Since pharmacological treatment options are limited and mainly directed at the bronchitis component, novel treatment strategies aiming at the restoration of damaged tissue are urgently awaited. The stem/progenitor cells responsible for lung tissue regeneration reside within their local microenvironment (the niche), which is composed of extracellular matrix and supportive stromal cells. In the healthy lungs, interactions within the microenvironment regulate repair mechanisms, which are compromised in emphysema. We hypothesize that restoring the healthy microenvironment of progenitor cells in the lung is critical for regenerative strategies targeted at improving lung function in emphysema. By using multi-omics data from patient cohorts and innovative patient-specific models, we will design new pharmacological strategies to restore defective interactions within the microenvironment and promote endogenous lung tissue regeneration by progenitor cells in an early stage of the disease. We will combine these pharmacological strategies with cell-based intervention strategies using stromal cells to improve the destroyed alveolar architecture in the end stage of the disease, a crucial step for endogenous tissue regeneration. Through the development of the required novel cell- and lung region-specific therapeutic delivery strategies, we aim to contribute to the restoration of lung function loss in emphysema patients.
cell-based therapy, Lung regeneration, patient-specific models, regenerative pharmacology, single cell resolution
Amsterdam UMC, Leiden Universitair Medisch Centrum (LUMC), Rijksuniversiteit Groningen (RUG), Universiteit Twente (UT), University of Applied Sciences Groningen, University of Applied Sciences Leiden, Utrecht University (UU)
|Organisation||University Medical Center Groningen (UMCG)|
|Name||Prof. dr. H.I. (Irene) Heijink|