Escarrer-Garau, GabrielMartín-Medina, AinaTruyols-Vives, JoanGómez-Bellvert, CristinaElowsson, LindaWestergren-Thorsson, GunillaMolina-Molina, MariaMercader-Barceló, JosepSala Llinàs, Ernest2024-10-092024-10-092024-01-16Escarrer-Garau G, Martín-Medina A, Truyols-Vives J, Gómez-Bellvert C, Elowsson L, Westergren-Thorsson G, et al. In Vivo and In Vitro Pro-Fibrotic Response of Lung-Resident Mesenchymal Stem Cells from Patients with Idiopathic Pulmonary Fibrosis. Cells. 2024 Jan 16;13(2).https://hdl.handle.net/20.500.13003/20222https://hdl.handle.net/20.500.12105/23826Lung-resident mesenchymal stem cells (LR-MSC) are thought to participate in idiopathic pulmonary fibrosis (IPF) by differentiating into myofibroblasts. On the other hand, LR-MSC in IPF patients present senescence-related features. It is unclear how they respond to a profibrotic environment. Here, we investigated the profibrotic response of LR-MSC isolated from IPF and control (CON) patients. LR-MSC were inoculated in mice 48 h after bleomycin (BLM) instillation to analyze their contribution to lung damage. In vitro, LR-MSC were exposed to TGFβ. Mice inoculated with IPF LR-MSC exhibited worse maintenance of their body weight. The instillation of either IPF or CON LR-MSC sustained BLM-induced histological lung damage, bronchoalveolar lavage fluid cell count, and the expression of the myofibroblast marker, extracellular matrix (ECM) proteins, and proinflammatory cytokines in the lungs. In vitro, IPF LR-MSC displayed higher basal protein levels of aSMA and fibronectin than CON LR-MSC. However, the TGFβ response in the expression of TGFβ, aSMA, and ECM genes was attenuated in IPF LR-MSC. In conclusion, IPF LR-MSC have acquired myofibroblastic features, but their capacity to further respond to profibrotic stimuli seems to be attenuated. In an advanced stage of the disease, LR-MSC may participate in disease progression owing to their limited ability to repair epithelial damage.enghttp://creativecommons.org/licenses/by/4.0/LungIdiopathic Pulmonary FibrosisAnimalsHumansExtracellular Matrix ProteinsBronchoalveolar Lavage FluidBleomycinTransforming Growth Factor betaMiceresearch articleAtribución 4.0 Internacional3824785113210.3390/cells1302016010.3390/cells130201602073-4409Cellsopen accessFactor de Crecimiento Transformador betaAnimalesProteínas de la Matriz ExtracelularHumanosLíquido del Lavado BronquioalveolarBleomicinaPulmónRatonesFibrosis Pulmonar Idiopática2-s2.0-851830862711151954700001L2028107107