PT  - JOURNAL ARTICLE
AU  - Gerald Burgstaller
AU  - Sarah Vierkotten
AU  - Melanie Königshoff
AU  - Oliver Eickelberg
TI  - Disease-derived extracellular matrix scaffolds instruct the transdifferentiation and migration of lung fibroblasts
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P3906
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P3906.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P3906.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Introduction:Migration of activated fibroblasts within the alveolar compartment, their transition to myofibroblasts, and extensive secretion of extracellular matrix (ECM) constituents are indicative for active fibrogenesis. Aims/Objectives: We investigated whether the ECM from fibrotic tissue can instruct the transdifferentiation and migration of reseeded primary and immortalized lung fibroblasts. Methods: Lung slices (300 µm vibratome cuts) from PBS-, elastase- or bleomycin-treated mice were decellularized by treatment with deionized water for 16 hours, 0.1 % SDS for 4h, 1 M NaCl for 2h and 30 µg/ml DNAse for 1h. Lung slices were repopulated with mouse MLg and primary lung fibroblasts (106 cells/ml). Results: Immunohisto- and immunofluorescence-stainings showed that the basic ECM structure was preserved after decellularization. 4D live-cell imaging revealed that cells attached and spread to the ECM scaffold. Airway structures and vessels were completely repopulated, demonstrating cell proliferation on the scaffold for as long as 9 days, corroborated by Ki67 staining. Fibroblasts attached to the ECM scaffold by forming Vinculin and Talin positive focal adhesions. Depending on their local ECM microenvironment in the slice, reseeded fibroblasts displayed a high plasticity in morphology and migration. Furthermore, transdifferentiation to aSMA positive fibroblasts was accumulated in the peripheral pleural area, partially in vessel/airway structures but rarely in the alveolar space.Conclusion:Fibroblasts seeded on decellularized lung scaffolds displayed a huge plasticity in morphology, migratory behavior and aSMA expression as a function of the ECM microenvironment.