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Macrophage Immunomodulation: The Gatekeeper for Mesenchymal Stem Cell Derived-Exosomes in Pulmonary Arterial Hypertension?

Division of Newborn Medicine, Boston Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
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Int. J. Mol. Sci. 2018, 19(9), 2534; https://doi.org/10.3390/ijms19092534
Received: 7 August 2018 / Revised: 21 August 2018 / Accepted: 22 August 2018 / Published: 27 August 2018
(This article belongs to the Special Issue Molecular Research on Pulmonary Hypertension)
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by remodeling of the pulmonary arteries, increased pulmonary infiltrates, loss of vascular cross-sectional area, and elevated pulmonary vascular resistance. Despite recent advances in the management of PAH, there is a pressing need for the development of new tools to effectively treat and reduce the risk of further complications. Dysregulated immunity underlies the development of PAH, and macrophages orchestrate both the initiation and resolution of pulmonary inflammation, thus, manipulation of lung macrophage function represents an attractive target for emerging immunomodulatory therapies, including cell-based approaches. Indeed, mesenchymal stem cell (MSC)-based therapies have shown promise, effectively modulating the macrophage fulcrum to favor an anti-inflammatory, pro-resolving phenotype, which is associated with both histological and functional benefits in preclinical models of pulmonary hypertension (PH). The complex interplay between immune system homeostasis and MSCs remains incompletely understood. Here, we highlight the importance of macrophage function in models of PH and summarize the development of MSC-based therapies, focusing on the significance of MSC exosomes (MEx) and the immunomodulatory and homeostatic mechanisms by which such therapies may afford their beneficial effects. View Full-Text
Keywords: exosomes; extracellular vesicles (EVs); pulmonary hypertension (PH); bronchopulmonary dysplasia (BPD); mesenchymal stem cells (MSCs); MSC exosomes (MEx); pulmonary arterial hypertension (PAH); macrophages; inflammation exosomes; extracellular vesicles (EVs); pulmonary hypertension (PH); bronchopulmonary dysplasia (BPD); mesenchymal stem cells (MSCs); MSC exosomes (MEx); pulmonary arterial hypertension (PAH); macrophages; inflammation
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Willis, G.R.; Fernandez-Gonzalez, A.; Reis, M.; Mitsialis, S.A.; Kourembanas, S. Macrophage Immunomodulation: The Gatekeeper for Mesenchymal Stem Cell Derived-Exosomes in Pulmonary Arterial Hypertension? Int. J. Mol. Sci. 2018, 19, 2534.

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