Fibrosis, which is caused by chronic inflammation, results in impaired tissue architecture and functions in many organs including the lung. Idiopathic pulmonary fibrosis (IPF), the most common lung fibrosis, is a chronic and progressive lung interstitial disease accompanied by the pathological diagnosis of usual interstitial pneumonia (UIP). The pathogenesis of IPF is complicated, but a number of factors, such as myofibroblasts, the extracellular matrix (ECM), inflammation, and genetic and environmental factors, are thought to be involved in the onset and progression of IPF. Despite the accumulated knowledge of IPF through basic and clinical research over the last decades, an effective medical therapy for IPF remains to be established. It leads to a median survival of 3 years, which is much worse than many types of cancer. One of the reasons why basic research has failed to yield an effective therapy for IPF in the clinical stage is that animal models including the well-characterized bleomycin installation model do not fully recapitulate the pathogenesis of IPF. Thus, further research with new insights and perspectives is necessary for future directions in IPF research.
We and our collaborators have investigated humanized mice models of lung fibrosis induced by the infusion of human IPF fibroblasts. Using the humanized models, we have examined both the pre-existing drug and novel therapeutic candidates for IPF. One of the new therapeutic candidates for IPF is adipose-derived mesenchymal stem cell (ADSC). Compared with bone marrow-derived mesenchymal stem cells (BDSCs), ADSCs have several advantages such as easy accessibility and minimal morbidity on harvest. Moreover, in our studies, ADSCs produce many kinds of effective cytokines against fibrosis and reduce collagen expression in IPF fibroblasts, which indicates that ADSCs would be a promising therapeutic candidate for IPF.
In this talk, we will discuss factors controlling lung fibrosis, future directions of IPF research to bring an effective therapy to the clinical stages, and the potential of ADSCs to treat IPF.