Proceedings: Regenerative Medicine for Lung Diseases: A CIRM Workshop Report

Abstract

The mission of the California Institute of Regenerative Medicine (CIRM) is to accelerate treatments to patients with unmet medical needs. In September 2016, CIRM sponsored a workshop held at the University of California, Los Angeles, to discuss regenerative medicine approaches for treatment of lung diseases and to identify the challenges remaining for advancing such treatments to the clinic and market approval. Workshop participants discussed current preclinical and clinical approaches to regenerative medicine in the lung, as well as the biology of lung stem cells and the role of stem cells in the etiology of various lung diseases. The outcome of this effort was the recognition that whereas transient cell delivery approaches are leading the way in the clinic, recent advances in the understanding of lung stem cell biology, in vitro and in vivo disease modeling, gene editing and replacement methods, and cell engraftment approaches raise the prospect of developing cures for some lung diseases in the foreseeable future. In addition, advances in in vitro modeling using lung organoids and "lung on a chip" technology are setting the stage for high quality small molecule drug screening to develop treatments for lung diseases with complex biology. Stem Cells Translational Medicine 2017;6:1823-1828.

Keywords: Bioengineering; Cellular therapeutics; Clinical trials; Disease modeling; Engraftment; Gene therapy; In vivo imaging; Induced pluripotent stem cells; Lung; Lung diseases; Mesenchymal stromal cells; Organoids; Regenerative medicine; Stem cells.

Figure 1

Regions of the lung, their potential stem cell niches and related lung diseases. Left: Regions of the bronchial tree are shown from proximal (top) to distal (bottom). Middle: The normal histology of regions highlighted in the blue boxes are shown, indicating putative, region‐specific stem/progenitor cells and their niches. Right: Lung diseases shown are (a): cystic fibrosis with mucus plugging and abnormal submucosal gland duct (arrow), (b): chronic obstructive pulmonary disease with squamous metaplasia (solid arrow) and mucus metaplasia (dotted arrow), (c): pulmonary arterial hypertension with intimal thickening (arrow), (d): acute respiratory distress syndrome with hyaline membranes (arrow), inflammation, and edema, (e): idiopathic pulmonary fibrosis with fibrotic foci (arrow) and extensive lung remodeling and (f): bronchopulmonary dysplasia with alveolar simplification. Abbreviations: ARDS, acute respiratory distress syndrome; BASC, bronchioalveolar stem cell; BPD, bronchopulmonary dysplasia; CF, cystic fibrosis; COPD, chronic obstructive pulmonary disease; IPF, idiopathic pulmonary fibrosis; LNEP, lineage‐negative epithelial stem/progenitor cell; PAH, pulmonary arterial hypertension; T2*, type 2 alveolar cell*.