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Many ultrafine particles comprised classically of low-toxicity, low-solubility materials such as carbon black and titanium dioxide have been found to have greater toxicity than larger, respirable particles made of the same material. The basis of the increased toxicity of the ultrafine form is not well understood and a programme of research has been carried out in Edinburgh on the toxicology of ultrafines aimed at understanding the mechanism. We used fine and ultrafine carbon black, TiO₂ and latex and showed that there was an approximately 10-fold increase in inflammation with the same mass of ultrafine compared with fine particles. Using latex particles in three sizes—64, 202 and 535 nm—revealed that the smallest particles (64 nm) were profoundly inflammogenic but that the 202 and 535 nm particles had much less activity, suggesting that the cut-off for ultrafine toxicity lies somewhere between 64 and 202 nm. Increased oxidative activity of the ultrafine particle surface was shown using the fluorescent molecule dichlorofluorescein confirming that oxidative stress is a likely process by which the ultrafines have their effects. However, studies with transition-metal chelators and soluble extracts showed that the oxidative stress of ultrafine carbon black is not necessarily due to transition metals. Changes in intracellular Ca²⁺ levels in macrophage-like cells after ultrafine particle exposure suggested one way by which ultrafines might have their pro-inflammogenic effects.

An increasing number of studies suggest that cell therapy approaches may be powerful tools for repair of injured or diseased lungs as well as for understanding mechanisms involved in both lung development and lung repair. This rapidly progressing field encompasses a number of disciplines and conceptual approaches including the study of endogenous stem and progenitor cells resident in the lung, and investigations utilizing exogenously administered cells for the repair of injured lung. Moreover, the field has undergone several conceptual shifts over recent years. For example, the initial focus on engraftment of exogenously administered cells as airway or alveolar epithelium has been shifted to the current emphases on immunomodulation of inflammatory and immune pathways in the lung by stem cells, and on bioengineering approaches to grow functional lung tissue ex vivo for subsequent use in in vivo implantation for destructive lung diseases, such as emphysema. Furthermore, it has become apparent that the variety of candidate stem and progenitor cell types can have different actions in the lung. Each of these areas is the focus of a comprehensive chapter in this book. The goal of this introductory chapter is to provide an overview of the field to date.