British medical bulletin
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The adult lung is a complex organ whose large surface area interfaces extensively with both the environment and circulatory system. Yet, in spite of the high potential for exposure to environmental or systemic harm, epithelial cell turnover in adult lung is comparatively slow. Moreover, loss of lung function with advancing age is becoming an increasingly costly healthcare problem. Cell-based therapies stimulating endogenous stem/progenitor cells or supplying exogenous ones have therefore become a prime translational goal. Alternatively when lung repair becomes impossible, replacement with tissue-engineered lung is an attractive emerging alternative using a decellularized matrix or bioengineered scaffold. ⋯ Lack of consensus on specific lineage markers for lung stem and progenitor cells in development and disease constrains transferability of research between laboratories and sources of cellular therapy. Furthermore, effectiveness of individual cellular therapies to correct gas exchange and provide other critical lung functions remains unproven. Finally, feasibility of autologous whole organ replacement has not been confirmed as a durable therapy. Growing points Cellular therapies for lung regeneration would be enhanced by better lineage tracing within the lung, the ability to direct differentiation of exogenous stem or progenitor cells, and the development of functional assays for cellular viability and regenerative properties. Whether endogenous or exogeneous cells will ultimately play a greater therapeutic role remains to be seen. Reducing the need for lung replacement via endogenous cell-mediated repair is a key goal. Thereafter, improving the potential of donor lungs in transplant recipients is a further area where cell-based therapies may be beneficial. Ultimately, lung replacement with autologous tissue-engineered lungs is another goal for cell-based therapy. Areas timely for developing research Defining 'lung stem or progenitor cell' populations in both animal models and human tissue may help. Additionally, standardizing assays for assessing the potential of endogenous or exogenous cells within the lung is important. Understanding cell-matrix interactions in real time and with biomechanical insight will be central for lung engineering. Cautionary note Communicating the real potential for cell-based lung therapy needs to remain realistic, given the keen expectations of patients with end-stage lung disease.