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

International Journal of Molecular Sciences
Gareth R WillisStella Kourembanas

Abstract

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 sig...Continue Reading

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Citations

Sep 13, 2019·Cell Transplantation·Yu YouZuo-Jin Liu
Mar 12, 2019·Current Stem Cell Research & Therapy·Wenjie ZhengWeixin Zhao
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Jul 13, 2021·Frontiers in Cell and Developmental Biology·Di LuQi Zhang
Oct 27, 2021·American Journal of Respiratory and Critical Care Medicine·Gareth R WillisStella Kourembanas

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Methods Mentioned

BETA
bronchoalveolar lavage
flow filtration
RNA-seq

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