Definition of the Status of the Human Lung Stem Cell Niches ex Vivo in Tissue Biopsies Performed in Patients With Emphysema and Interstitial Fibrosis Compared to Non-diseased Areas

Scientific Background

Degenerative lung disorders are the result of inflammatory events that end in destruction of the normal pulmonary architecture. Two main patterns exist:

1. Chronic obstructive lung disease (COPD) is a major cause of morbidity and mortality. Until 2020 it is expected to become the third cause of mortality following cardiovascular disorders and cancer. Emphysema is the destructive form of COPD as the alveolated tissue disappears. This anatomic pattern is not always homogenous and functional impairment is not connected to the extent of the tissue destruction. Therapeutic elimination of the destroyed tissue may be achieved by surgery or by using various blocking techniques (Lung Volume Reduction).
2. Pulmonary fibrosis (PF) is characterized by abnormal repair of the respiratory epithelium. Various diseases may result in PF such as infections, autoimmune (connective tissue disorders), sarcoidosis, hypersensitivity pneumonitis, pneumoconiosis, histiocytosis X, lymphangioleiomyomatosis LAM etc. In many situations a cause effect relationship cannot be identified and the disease is idiopathic IPF.

During the last years cell based therapies using progenitor cells and various scaffolds became available in various medical fields. Lung regenerative medicine appears to be an alternative to transplantation in these end-stage diseases.

However, very complex cellular composition of the lung, comprising more than 40 different cell types, makes this objective challenging. The epithelial lining of the respiratory tract, composed of conducting and respiratory parts, varies along its proximo-distal axis. The conducting airways from the trachea to bronchioles of human lungs consist of pseudostratified epithelium, comprising equal proportions of basal cells, secretory cells, and ciliated cells, as well as some neuroendocrine cells. The smallest bronchioles, known as terminal and respiratory bronchioles, are lined with a simple columnar or cuboidal epithelium containing secretory and ciliated cells with fewer basal cells. The epithelia of these conducting airways form a tight barrier against the outside world and are specialized for the process of mucociliary clearance. The alveoli are lined by type 1 and 2 alveolar epithelial cells, called AT1 and AT2, respectively, hereafter. These cells are also specialized for barrier function and the extremely thin AEC1s share a basement membrane with the surrounding network of pulmonary capillaries to facilitate the diffusion of gases between the atmosphere and the circulation.