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Frontiers of Medicine >> 2020, Volume 14, Issue 3 doi: 10.1007/s11684-019-0717-5

Evidence for lung repair and regeneration in humans: key stem cells and therapeutic functions of fibroblast growth factors

. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.. Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.. Institute of Life Sciences, Wenzhou University, Wenzhou 325035, China.. Cardio-Pulmonary Institute, Universities of Giessen and Marburg Lung Center, member of the German Center for Lung Research, Justus-Liebig-University Giessen, 35392 Giessen, Germany

Accepted: 2019-11-19 Available online: 2019-11-19

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Regeneration carries the idea of regrowing partially or completely a missing organ. Repair, on the other hand, allows restoring the function of an existing but failing organ. The recognition that human lungs can both repair and regenerate is quite novel, the concept has not been widely used to treat patients. We present evidence that the human adult lung does repair and regenerate and introduce different ways to harness this power. Various types of lung stem cells are capable of proliferating and differentiating upon injury driving the repair/regeneration process. Injury models, primarily in mice, combined with lineage tracing studies, have allowed the identification of these important cells. Some of these cells, such as basal cells, broncho-alveolar stem cells, and alveolar type 2 cells, rely on fibroblast growth factor (FGF) signaling for their survival, proliferation and/or differentiation. While pre-clinical studies have shown the therapeutic benefits of FGFs, a recent clinical trial for acute respiratory distress syndrome (ARDS) using intravenous injection of FGF7 did not report the expected beneficial effects. We discuss the potential reasons for these negative results and propose the rationale for new approaches for future clinical trials, such as delivery of FGFs to the damaged lungs through efficient inhalation systems, which may be more promising than systemic exposure to FGFs. While this change in the administration route presents a challenge, the therapeutic promises displayed by FGFs are worth the effort.

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