Adipose Tissue-Derived Stem Cells Have the Ability to Differentiate into Alveolar Epithelial Cells and Ameliorate Lung Injury Caused by Elastase-Induced Emphysema in Mice

Abstract

Chronic obstructive pulmonary disease is a leading cause of mortality globally, with no effective therapy yet established. Adipose tissue-derived stem cells (ADSCs) are useful for ameliorating lung injury in animal models. However, whether ADSCs differentiate into functional cells remains uncertain, and no study has reported on the mechanism by which ADSCs improve lung functionality. Thus, in this study, we examined whether ADSCs differentiate into lung alveolar cells and are able to ameliorate lung injury caused by elastase-induced emphysema in model mice. Here, we induced ADSCs to differentiate into type 2 alveolar epithelial cells in vitro. We demonstrated that ADSCs can differentiate into type 2 alveolar epithelial cells in an elastase-induced emphysematous lung and that ADSCs improve pulmonary function of emphysema model mice, as determined with spirometry and 129Xe MRI. These data revealed a novel function for ADSCs in promoting repair of the damaged lung by direct differentiation into alveolar epithelial cells.

Potential Using of Fat-derived Stromal Cells in the Treatment of Active Disease, and also, in Both Pre- and Post-Periods in COVID-19

“…Compared with BM-MSCs, ASCs have a higher differentiation capacity, proliferation rate, and regenerative potential [14]. Adipose derived stromal cells have high immunomodulating capacity and can ameliorate lung injury by secreting several factors with paracrine effects of several growth factors, such as hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) [15]. It has been proven that ADSCs have beneficial effects in animal models of pulmonary diseases such as COPD, ARDS, bronchiolitis obliterans, idiopathic pulmonary fibrosis and emphysema [14].…”

“…It has been proven that ADSCs have beneficial effects in animal models of pulmonary diseases such as COPD, ARDS, bronchiolitis obliterans, idiopathic pulmonary fibrosis and emphysema [14]. These paracrine effects promote the proliferation of alveolar epithelial cells and angiogenesis and inhibit cell apoptosis [15]. ADCs will have the greatest support in the treatment of COVID 19, especially in terms of lung involvement, in terms of type 2 alveolar cell regeneration.…”

New normal: two aspects of adipose tissue in COVID-19—treat and threat?

“…Because there are many studies supporting this argument in the literature. Fukui et al, showed that that ADSCs differentiate into type 2 alveolar epithelial cells [24]. Additionally, ADSCs seem to have greater antiinflammatory potential than BM-MSCs, since they secrete higher levels of bioactive mediators, and have been shown to attenuate lung inflammation in different models of lung injury [25].…”

“…Additionally, ADSCs seem to have greater antiinflammatory potential than BM-MSCs, since they secrete higher levels of bioactive mediators, and have been shown to attenuate lung inflammation in different models of lung injury [25]. In experimental pulmonary system models, the causes of unsuccessful MSC treatment have been reported as insufficient cell number, condition of cells, cell types, frequency and timing of administration, and insufficient doses of administration [24,26] These problems can be solved with stromal cells from adipose tissue. Because a large number of cells can be obtained in high quality and not only as MSC, but also as a cocktail with other stromal cells.…”

“…T-suppressor [33] The ability of ADSCs to regulate and influence the frequency and activity of T cells, B cells, and macrophages has been documented in numerous in vitro coculture systems and in vivo models. ASCs, similar to BM-MSCs, inhibited allogeneic lymphocyte proliferation in mixed lymphocyte cultures through cell-cell contact; one of the possible mechanisms mediating the immunosuppressive effect of ASCs is via stimulating the production of functional de novo regulatory T cells [24]. Immunoregulation of ASCs is based on direct cell-cell contact with immune cells associated with paracrine secretion of soluble mediators, cytokines, and growth factors [33].…”