Stem cell-based therapy for pulmonary fibrosis

Abstract Pulmonary fibrosis (PF) is a chronic and relentlessly progressive interstitial lung disease in which the accumulation of fibroblasts and extracellular matrix (ECM) induces the destruction of normal alveolar structures, ultimately leading to respiratory failure. Patients with advanced PF are unable to perform physical labor and often have concomitant cough and dyspnea, which markedly impair their quality of life. However, there is a paucity of available pharmacological therapies, and to date, lung transplantation remains the only possible treatment for patients suffering from end-stage PF; moreover, the complexity of transplantation surgery and the paucity of donors greatly restrict the application of this treatment. Therefore, there is a pressing need for alternative therapeutic strategies for this complex disease. Due to their capacity for pluripotency and paracrine actions, stem cells are promising therapeutic agents for the treatment of interstitial lung disease, and an extensive body of literature supports the therapeutic efficacy of stem cells in lung fibrosis. Although stem cell transplantation may play an important role in the treatment of PF, some key issues, such as safety and therapeutic efficacy, remain to be resolved. In this review, we summarize recent preclinical and clinical studies on the stem cell-mediated regeneration of fibrotic lungs and present an analysis of concerning issues related to stem cell therapy to guide therapeutic development for this complex disease.