Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. As fibrosis thickens, the lung tissue loses the ability to facilitate gas exchange and provide cells with needed oxygen. Currently, IPF has few treatment options and no effective therapies, aside from lung transplant. Here we present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. Analysis reveals that LSC-Sec and LSC-Exo treatments could attenuate and resolve bleomycin- and silica-induced fibrosis by reestablishing normal alveolar structure and decreasing both collagen accumulation and myofibroblast proliferation. Additionally, LSC-Sec and LSC-Exo exhibit superior therapeutic benefits than their counterparts derived from mesenchymal stem cells in some measures. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation
It has been reported that the mesenchymal stem cell secretome (MSC-Sec), or conditioned media, reproduces the therapeutic effects seen in MSC cell therapy in some diseases, such as osteoarthritis, bronchopulmonary dysplasia, and multiple sclerosis[4,5,6]
Fibrosis progression in IPF patients is widely unknown and is vastly different from one patient to the but our previous experience with the Bleo model showed that inflammation peaks around day seven post injection and transitions to a more fibrogenic phase around day nine dominated by deposition of extracellular matrix and destruction of the alveolar structures[1,16]
Summary
Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable form of interstitial lung disease in which persistent injury results in scar tissue formation. We present a series of studies utilizing lung spheroid cell-secretome (LSC-Sec) and exosomes (LSC-Exo) by inhalation to treat different models of lung injury and fibrosis. We showed that an inhalation treatment of secretome and exosome exhibited therapeutic potential for lung regeneration in two experimental models of pulmonary fibrosis. The purpose of the present study is to examine the therapeutic effects of lung spheroid cell secretome (LSC-Sec) in pulmonary fibrosis. It has been reported that the mesenchymal stem cell secretome (MSC-Sec), or conditioned media, reproduces the therapeutic effects seen in MSC cell therapy in some diseases, such as osteoarthritis, bronchopulmonary dysplasia, and multiple sclerosis[4,5,6]. Our over-arching hypothesis is that lung spheroid cell secretome (LSC-Sec) promotes lung repair in pulmonary fibrosis, in a fashion superior to its MSC counterpart
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