29 April 2019

TISSUE SPOTLIGHT: Lung

Karen McAulay

By Karen McAulay

Karen McAulay, Ph.D.
Clinical Alliance Manager, REPROCELL

Drug Discovery, Human Tissues, Tissue Spotlight, Lung  

REPROCELL-Tissue-Spotlight

This issue, we are casting the REPROCELL Tissue Spotlight on the LUNG.

lungs-renderingThe lungs are the central organs of the human respiratory system enabling you to take around 25,000 breaths a day — mostly, without any conscious thought that you are doing so!

 

The human respiratory system consists of an upper (nasal cavity, pharynx and larynx) and lower area (trachea, bronchi, bronchioles and the lungs) that work together to oversee the 6 main functions of the system, namely, pulmonary ventilation, external respiration, internal respiration, protection from infection, the creation of sound and smell (table 1).

Humans have evolved to contain two lungs within the system. Due to the physical constraints within the thoracic cavity, one is slightly larger than the other with three lobes or sections, whilst the smaller lung only has two lobes. Within each lobe the bronchioles divide into alveolar ducts which give rise to the microscopic sacs or alveoli, essential for the respiration function of the system and for providing the sponge like quality of lung tissue. It is estimated that both lungs together contain over 2000 kms of airways and around 500 million alveoli — enough to cover an area the size of a tennis court!

 

Table 1: Main Functions of the Respiratory System
Function How it works
Pulmonary Ventilation (Breathing) Air is inhaled through the nose and mouth, travels through the upper respiratory region into the lung. Air is exhaled back through this pathway. Changes to the volume and air pressure within the lungs trigger pulmonary ventilation with the diaphragm and intercostal muscles contracting and relaxing to facilitate the process.
External Respiration External respiration results in the exchange of oxygen for carbon dioxide within the lung. The process takes place between the millions of alveoli and the pulmonary capillaries that surround them. Oxygen from inhaled air diffuses through the alveoli into the capillary where it binds to red blood cells. Carbon dioxide from de-oxygenated blood diffuses from the blood cells into the alveoli and is released back into the air upon exhalation.
Internal Respiration Internal respiration exchanges gases between blood cells and tissues. Red blood cells carry oxygen around the body. When they reach the narrowest point of the system — the capillaries — release the oxygen to diffuse through the capillary wall into the tissue. Carbon dioxide is exchanged back in the process.
Pathogen Protection Lined with hair-like projections called cilia that move microbes and debris up and out of the airways, the bronchial sections of the system are crucial for protection. Scattered throughout the cilia are also goblet cells that secrete mucus which helps to protect the lining of the bronchus and trap microorganisms.
Sound Creation Phonation is the creation of sound by structures of the respiratory tract. When we speak muscles of the larynx move and push the vocal cords. Air passing through makes the cords vibrate, creating sound. The degree of ‘push’ on the cords can alter the vibrations and change the pitch of the sound.
Olfaction (smell) Olfaction or smelling begins in the nasal cavity. As air enters chemicals in the air bind and stimulate receptors within the upper respiratory tract. A signal is then sent from the nasal cavity through the olfactory bulbs to the olfactory area of the brain. Recognition by the brain is what we would call smell.

 

Due to delicate nature of lung tissue and the tapering architecture of the airways, the lungs can be susceptible to various diseases and conditions. They are particularly vulnerable to infection and injury from the external environment because of constant exposure to air and associated particulates. Lung disease can be crudely classified into three subtypes: airway disease, lung tissue disease and lung circulation disease.

 

Types of Lung Disease

Airway diseases: affect the airways that carry gases in and out of the lung. They usually cause a narrowing or blockage and include diseases such as Asthma and Chronic Obstructive Pulmonary Disease (COPD).

Lung Tissue Diseases: affect the structure of the lung. Scarring or inflammation of the tissue make expansion of the lungs during breathing difficult i.e., they are restrictive. Pulmonary Fibrosis and Sarcoidosis are good examples of lung tissue disease.

Lung Circulation diseases: affect the blood vessels in the lungs, usually through clotting, scarring or inflammation, e.g. Hypertension. They affect the ability of the lung to exchange gases.

 

In the UK, around 10,000 cases of lung disease are newly diagnosed each year. It is estimated that around 1 in 5 individuals in the UK suffer from a long-term respiratory illness such as asthma or COPD, and the burden on the National Health Service is huge, with upwards of half a million hospital admissions each year. Globally, respiratory diseases impose an immense burden on health care with five respiratory diseases among the most common causes of severe illness and death worldwide (table 2). Other respiratory disease where the burden is great, but estimates are more difficult to discern, include sleep-disordered breathing, pulmonary hypertension and occupational lung disease, all of which affect millions of individuals worldwide. Inclusive of all respiratory disease, estimates suggest that over 1 billion people suffer either from acute or chronic respiratory conditions.

Current treatments and controls, for example, inhalers, steroids, oxygen treatment, vaccines, antibiotics, clean air measures, smoking cessation etc., can be effective in treating some conditions or alleviating symptoms, however, even with such treatments, lung disease still accounts for approximately 20% of all deaths in the UK, and 1 in 6 deaths worldwide. Research into the pathogenesis of conditions and the development of new and effective treatments is therefore a high priority from a global health perspective and is a primary focus for many researchers.

 

Table 2: Top 5 Respiratory Diseases Worldwide
Disease Prevalence (WHO estimates)
COPD ~65 million moderate to severe cases; ~3 million deaths/year; 3rd leading cause of death worldwide
Asthma ~300 million cases; affecting 14% of children globally
Acute Infection ~4 million deaths /year; leading cause of death in young children
Tuberculosis ~10 million affected/year; ~1 million deaths annually
Lung Cancer  Most common neoplasm worldwide; ~1.5 million deaths yearly

 

REPROCELL is leading the way in the provision of biologically relevant custom drug-discovery assays to aid researchers in this goal.

How can REPROCELL help your respiratory system research?

By accessing and using ethically sourced and consented human tissues, REPROCELL is able to provide indications of drug safety, efficacy and absorption during the drug development process.

  • Bronchodilation/constriction
  • Ion channel function (epithelial secretion)
  • Inflammatory response
  • Absorption

REPROCELL can investigate the effects of novel compounds on the respiratory system in a number of ways, thus, helping researchers to meet the ICH safety pharmacology requirements for human pharmaceuticals. Through our Tissue Network access to surplus surgical and non-transplantable tissue, we can isolate fresh tissue from different regions of the respiratory system, including upper airways, secondary/tertiary bronchi or parenchyma, for use in our respiratory assays and studies. Compared to more traditional animal-based models, such human tissue-based test systems better reflect the human response and provide more biologically relevant information with respect to potential therapies. 

REPROCELL Respiratory System Assays

Airway Contractility
Effect of compounds on the dilation or constriction properties of airways assessed using fresh bronchial tissue mounted in organ bath/myograph systems.

Precision Cut Lung Slice (PCLS)
PCLS retains the structural and functional integrity of the tissue. Identical slices are cultured in the presence of compounds to assay biomarker release, structural integrity, tissue viability and inflammation process.

Respiratory Channel Function (ADME)
Effect of compounds upon movement through the epithelial membrane assessed using lung or tracheal epithelial tissue mounted in a Ussing Chamber system.

Parenchyma Culture
A parenchymal explant culture system where cell ratios and spatial orientation are maintained allowing cell-cell communication and interaction. Local effects of test compounds can be assessed.

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