Increased In Vitro Intercellular Barrier Function of Lung Epithelial Cells Using Adipose-Derived Mesenchymal Stem/Stromal Cells

Abstract

With the emergence of coronavirus disease-2019, researchers have gained interest in the therapeutic efficacy of mesenchymal stem/stromal cells (MSCs) in acute respiratory distress syndrome; however, the mechanisms of the therapeutic effects of MSCs are unclear. We have previously reported that adipose-derived MSCs (AD-MSCs) strengthen the barrier function of the pulmonary vessels in scaffold-based bioengineered rat lungs. In this study, we evaluated whether AD-MSCs could enhance the intercellular barrier function of lung epithelial cells in vitro using a transwell coculture system. Transepithelial electrical resistance (TEER) measurements revealed that the peak TEER value was significantly higher in the AD-MSC coculture group than in the AD-MSC non-coculture group. Similarly, the permeability coefficient was significantly decreased in the AD-MSC coculture group compared to that in the AD-MSC non-coculture group. Immunostaining of insert membranes showed that zonula occuldens-1 expression was significantly high at cell junctions in the AD-MSC coculture group. Moreover, cell junction-related gene profiling showed that the expression of some claudin genes, including claudin-4, was upregulated in the AD-MSC coculture group. Taken together, these results showed that AD-MSCs enhanced the barrier function between lung epithelial cells, suggesting that both direct adhesion and indirect paracrine effects strengthened the barrier function of lung alveolar epithelium in vitro.

Mesenchymal cells support the early retention of primary alveolar type 2 cells on acellular mouse lung scaffolds

“…Indeed, previous work has suggested that AT2 cells are located near Pdgfra + mesenchymal cells, which promote AT2 self-renewal and differentiation into AT1 cells [ 24 ]. Moreover, paracrine signaling from mesenchymal populations can also provide therapeutic effects [ 21 , 25 ]. For instance, MSCs enhanced the barrier function in lung epithelial cells in a transwell culture model in which epithelial cells were grown in both direct and indirect contact conditions.…”

“…For instance, MSCs enhanced the barrier function in lung epithelial cells in a transwell culture model in which epithelial cells were grown in both direct and indirect contact conditions. Authors concluded that both direct adhesion and indirect paracrine effects strengthened the barrier function of lung alveolar epithelium in vitro [ 25 ]. Thus, it is likely that in this study, he initial support provided by BMC was can be attributed to potential direct cell to cell contact with AT2 cells as well as via paracrine signaling of neighbouring MSCs retained in the scaffold.…”

Role of DCLK1/Hippo Pathway in Type II Alveolar Epithelial Cells Differentiation in Acute Respiratory Distress Syndrome

“…Furthermore, we observed a decrease in TEER in AECII at 4 h, followed by an increase at 6 h after YAP inhibition. The initial reduction in TEER indicates increased cell permeability due to AECII destruction (Metz et al 2020), and the subsequent increase in TEER could be due to the restoration of intercellular junctions among the cells resulting from AECII-to-AECI differentiation (Ishii et al 2021). The dynamic control of YAP appears to balance the degradation and reconstruction of alveolar epithelial integrity during AECII differentiation.…”