Abstract

Mesenchymal Stem Cell Exosomes: Powerful Agents of Lung Growth and Repair

Stella Kourembanas, Chief, Division of Newborn Medicine, Boston Children’s Hospital; Clement A. Smith Professor of Pediatrics, Harvard Medical School

Bronchopulmonary dysplasia (BPD) is the most common complication of prematurity characterized by an arrest of lung growth with reduced alveoli, fewer blood vessels, and abnormal lung function. BPD has significant long-term pulmonary morbidities, including pulmonary hypertension (PH), airway hyperreactivity, abnormal pulmonary function test results, and, in some cases, emphysematous changes that persist into adulthood. Mesenchymal stem cells (MSCs) are recognized as potential cell-based therapy for diseases of the lung. These multipotent cells exhibit beneficial effects through anti-inflammatory, immuno-modulatory, pro-survival and anti-fibrotic mechanisms that are not clearly defined. We showed that bone marrow-derived MSCs or their cell-free conditioned media (CM) prevent and reverse experimental lung injury in the neonatal mouse model of BPD. We isolated exosomes from human MSC-CM and showed that they can prevent lung inflammation and PH in experimental models. Exosomes are small vesicular structures produced by all cells that contain a distinct cargo which not only represents the cell of origin but is differentially-enriched in specific nucleic acid or lipid/protein species. They serve as an important cell-to-cell communication mechanism. We have shown that MSC exosomes restore lung homeostasis through immuno-modulatory pathways, and enable lung-specific progenitor cells to repair lung injury. Current work is focusing on the full characterization of MSC exosomes and their biological function in lung injury, growth, and repair using experimental models of broncho-pulmonary dysplasia. Our goal is to develop the most optimal, well-characterized, and functional MSC exosome preparation for human application.