Cargando…

Macrophage Immunomodulation: The Gatekeeper for Mesenchymal Stem Cell Derived-Exosomes in Pulmonary Arterial 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 press...

Descripción completa

Detalles Bibliográficos
Autores principales: Willis, Gareth R., Fernandez-Gonzalez, Angeles, Reis, Monica, Mitsialis, S. Alex, Kourembanas, Stella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164282/
https://www.ncbi.nlm.nih.gov/pubmed/30150544
http://dx.doi.org/10.3390/ijms19092534
Descripción
Sumario: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.