Unraveling Alveolar Fibroblast and Activated Myofibroblast Heterogeneity and Differentiation Trajectories During Lung Fibrosis Development and Resolution in Young and Old Mice.
Aging cell
View this publicationThe Vazquez-Armendariz lab primarily focuses on the use of three-dimensional lung organoid systems from murine and human adult somatic stem cells and human induced pluripotent stem cells (iPSCs) to model lung development and disease.
In our previous published work, we developed a robust and reliable protocol for the generation of murine bronchioalveolar lung organoids (BALO). This model was generated by FACS cell sorting and co-cultivation of bronchoalveolar epithelial stem cells and resident mesenchymal cells isolated from the lung homogenate of adult mice. After 21 days of culture, BALO spatially organized in bronchiolar and alveolar regions with airway-like structures containing basal cells, secretory, and ciliated cells while alveolar-like regions differentiate into mature alveolar epithelial cell type 1 and type 2. In addition, we have successfully standardized a microinjection technique that permits the direct addition of immune cells such as alveolar macrophages and monocytes within the lung organoids allowing investigation of cell-specific crosstalk/interactions occurring during viral injury and repair. Moreover, this model is well-suited to support infection and replication of selected respiratory viruses such as influenza (IAV). Direct infection of BALO epithelium with different strains of IAV not only supports viral spread and replication but also elicits an enhanced antiviral immune response when micro-injected alveolar macrophages are present. Notably, microinjection of IAV into BALO airway-like structures recapitulates proximal-to-distal spread of the infection and causes substantial loss of AEC in the infected alveolar-like areas, thus, mimicking this aspect of IAV pneumonia. Another major aim from our lab is the establishment of a human iPSC-derived lung organoid platform closely resembling the lung architecture that could be used as meaningful tools for disease modeling and in regenerative medicine.
Ultimately, our research goal is to dissect the cellular and molecular crosstalk between lung epithelium and immune cells occurring during lung development, infection, injury and repair; especially, our lab aims at identifying the microenvironmental factors that determine macrophage phenotype during alveolar niche development and replenishment after injury.
Recent publications
-
-
Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury.
Cell reports
View this publication -
Evidence for a lipofibroblast-to- + myofibroblast reversible switch during the development and resolution of lung fibrosis in young mice.
The European respiratory journal
View this publication