Development of therapeutic extracellular vesicles for the treatment of acute and chronic lung diseases

Abstract

Acute and chronic lung diseases are among the most common causes of disability and death worldwide, which consequently contribute a substantial burden for health and economic system. Chronic obstructive pulmonary disease (COPD) – one type of chronic lung diseases – is a complicated and life-threatening disease. Despite considerable efforts toward developing treatments for COPD, there are currently no effective treatments to resolve this disease. The only available treatments are supportive, and they either allow for temporary relief of several symptoms of COPD such as dyspnoea, cough, and sputum, or reduce exacerbations. Hence, there is an urgent need for a new regenerative medicine approach that can promote the repair/regeneration process in lungs. In the context of tissue regeneration, extracellular vesicles (EVs) are considered as the next generation therapeutics, which can regenerate and restore the function of lung tissue that has been damaged by a disease or injury. However, very few EV-therapeutics can progress to clinical trials due to (a) the lack of standardisation of EV production, and (b) the lack of appropriate lung models to validate the therapeutic effects of EVs. Hence, to accelerate the clinical translation of EV-therapeutics to resolve COPD, the presented work in this thesis was divided into two stages: 1. Development of EV-therapeutics and establishing quality control protocol for EVs to ensure their safety and efficacy in treating COPD. 2. Establishing pre-clinical models to enable testing and validation of the efficacy of EV-therapeutics in treating COPD. This research provided an innovative methodology to produce and comprehensively characterise EVs, which offers a new means to understand the role of EVs in numerous biological processes and disease mechanisms. Moreover, this research would bring significant benefits to global healthcare by accelerating the development of EV-therapeutics for the treatment of lung diseases.