How has biotechnology found a potential cure to emphysema?
Answers
A new device intended to treat breathing difficulty associated with severe emphysema has been approved by the FDA. The device, Pulmonx's Zephyr Endobronchial Valve (Zephyr Valve) is a less invasive treatment than options currently available to patients.
Background
Chronic obstructive pulmonary disease presents with two different phenotypes: chronic bronchitis and emphysema with parenchymal destruction. Decreased expression of vascular endothelial growth factor and increased endothelial cell apoptosis are considered major factors for emphysema. Stem cells have the ability of vascular regeneration and function as a repair mechanism for the damaged endothelial cells. Currently, minimally invasive interventional procedures such as placement of valves, bio-foam or coils are performed in order to improve the disturbed mechanical function in emphysema patients. However, these procedures cannot restore functional lung tissue. Additionally stem cell instillation into the parenchyma has been used in clinical studies aiming to improve overall respiratory function and quality of life.
Methods
In our current experiment we induced emphysema with a DDMC non-viral vector in BALBC mice and simultaneously instilled stem cells testing the hyposthesis that they might have a protective role against the development of emphysema. The mice were divided into four groups: a) control, b) 50.000 cells, c) 75.000 and d) 100.000 cells.
Results
Lung pathological findings revealed that all treatment groups had less damage compared to the control group. Additionally, we observed that emphysema lesions were less around vessels in an area of 10 μm.
Conclusions
Our findings indicate that stem cell instillation can have a regenerative role if applied upon a tissue scaffold with vessel around.
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and progressive destruction of lung parenchyma. Currently there are no interventions able to reverse or even stop disease progression. Transplantation is the only option to regain functional tissue. Full medical treatment and smoking cessation are able to slow the progression of emphysema, improve quality of life and prolong survival [1]. Surgical lung volume reduction reduces hyperinflation and improves overall functional status although lung tissue is sacrificed. This approach is considered feasible for patients with predominantly upper lobe emphysema. In order to avoid surgery, minimally invasive interventional bronchoscopy techniques have been developed. The application of endobronchial valves, coils and bio-foam have been recently added as arrows in the quiver for emphysema treatment [2-4]. Despite all pharmaceutical or interventional treatment modalities the loss of lung tissue and remodeling continues [5,6]. Chronic obstructive pulmonary disease involves airways of all generations, the alveoli (<2 mm) and the tissue beyond. The major dysfunction observed clinically is the change of airflow parameters due to the loss of elastic lung recoil. Furthermore; endothelial dysfunction and vascular remodeling are initiated by vascular endothelial growth factor (VEGF)-mediated apoptosis [7]. Inflammatory response is also initiated by exposure to environmental factors such as; air pollution and cigarette smoking. Key factors in the destructive cascades are proteolytic substances and oxidant stress [8,9]. The irreversible process is further accelerated by frequent exacerbations. Despite the removal of the trigger factor, the inflammatory cells (neutrophils, macrophages and lymphocytes) still remain in large numbers within the respiratory airways and stimulate inflammation, remodeling and destruction, due to nature of the continuous exposure [10,11]. The airway epithelium has slow proliferative and renewal capability, unless injured [12]. While differentiated cells cannot compensate for the loss of complex lung tissue destroyed by the above outline processes, stem cells may have these capabilities. Stem cells have the ability of self-renewal and through trophic units they are mobilized and attracted to the site of damage [13]. Stem cells can be classified according to their potency to differentiate, in: unipotent stem cells, able to produce only one cell type, multipotent cells able to form all cells of one particular lineage, pluripotent stem cells capable of differentiating into any of the embryonic germ layers [14]. Finally, there are totipotent cells that can give rise to an entire organism. This property is retained in mammals by the zygote and up to at least 4-cell stage embryo [15-17].
Stem cells are also classified in embryonic stem cells and adult (ASCs) or non embryonic stem cells. The pluripotent embryonic stem cells derived from the inner cell mass of the blastocyst have the unique capacity to generate any cell of the body. Additionally they can stay as undifferentiated cell type for prolonged period of time in culture [16,18,19]. Adult stem cells (ACSs) have self-renewal capability, they are multipotent cells obtained from adult tissues.