TY - JOUR
T1 - Increased in vitro intercellular barrier function of lung epithelial cells using adipose-derived mesenchymal stem/stromal cells
AU - Ishii, Mitsutoshi
AU - Tsuchiya, Tomoshi
AU - Doi, Ryoichiro
AU - Morofuji, Yoichi
AU - Fujimoto, Takashi
AU - Muto, Hideki
AU - Suematsu, Takashi
AU - Mori, Ryoichi
AU - Matsumoto, Keitaro
AU - Miyazaki, Takuro
AU - Tomoshige, Koichi
AU - Watanabe, Hironosuke
AU - Iwatake, Mayumi
AU - Nagayasu, Takeshi
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8
Y1 - 2021/8
N2 - 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 syn-drome; 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 cocul-ture 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.
AB - 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 syn-drome; 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 cocul-ture 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.
KW - Acute respiratory distress syndrome
KW - Air-blood bar-rier
KW - Alveolar epithelial cell
KW - Barrier function
KW - Mesenchymal stem/stromal cell
KW - Transepithelial electrical resistance
UR - http://www.scopus.com/inward/record.url?scp=85113408874&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics13081264
DO - 10.3390/pharmaceutics13081264
M3 - 学術論文
C2 - 34452225
AN - SCOPUS:85113408874
SN - 1999-4923
VL - 13
JO - Pharmaceutics
JF - Pharmaceutics
IS - 8
M1 - 1264
ER -