TY - JOUR
T1 - Fetal mesenchymal stem cells ameliorate acute lung injury in a rat cardiopulmonary bypass model
AU - Taki, Tomofumi
AU - Masumoto, Hidetoshi
AU - Funamoto, Masaki
AU - Minakata, Kenji
AU - Yamazaki, Kazuhiro
AU - Ikeda, Tadashi
AU - Sakata, Ryuzo
N1 - Publisher Copyright:
© 2016 The American Association for Thoracic Surgery
PY - 2017/3/1
Y1 - 2017/3/1
N2 - Background Systemic inflammation after prolonged cardiopulmonary bypass (CPB) can cause serious multiorgan system dysfunction. Mesenchymal stem cells (MSCs) are reported to reduce inflammation and attenuate immune response. We have focused on fetal membrane (FM) as a source to provide a large number of MSCs (FM-MSCs). Allogeneic administration of FM-MSCs has been reported to mitigate autoimmune myocarditis or glomerulonephritis. The aim of this study was to investigate whether allogeneic FM-MSCs attenuate systemic inflammatory responses and lung injury in a rat CPB model. Methods Male Lewis rats (major histocompatibility complex haplotype: RT-1l) were divided randomly into 3 groups (n = 7 each): cannulation alone (sham group), CPB alone (control group), and CPB + MSC (MSC group). An experimental rat CPB model was established, and CPB was maintained for 30 minutes. In the MSC group, MSCs (1 × 106 cells) derived from the FM of ACI rats with a different major histocompatibility complex haplotype (RT-1a) were administrated intravenously before CPB initiation. Results Serum concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1β in the MSC group were significantly lower compared with the control group after CPB. Similarly, mRNA expression of proinflammatory cytokines in the lung was lower in the MSC group. Allogeneic administration of FM-MSCs remarkably decreased the lung injury score, protected alveolar structure, inhibited neutrophil infiltration to the lung interstitium, and stimulated cytoprotective cytokine production in the lung. Conclusions Allogeneic transplantation of FM-MSCs may be a potent strategy to prevent CPB-induced systemic inflammation and acute lung injury by suppressing the expression of inflammatory cytokines and promoting protective factors in the lung.
AB - Background Systemic inflammation after prolonged cardiopulmonary bypass (CPB) can cause serious multiorgan system dysfunction. Mesenchymal stem cells (MSCs) are reported to reduce inflammation and attenuate immune response. We have focused on fetal membrane (FM) as a source to provide a large number of MSCs (FM-MSCs). Allogeneic administration of FM-MSCs has been reported to mitigate autoimmune myocarditis or glomerulonephritis. The aim of this study was to investigate whether allogeneic FM-MSCs attenuate systemic inflammatory responses and lung injury in a rat CPB model. Methods Male Lewis rats (major histocompatibility complex haplotype: RT-1l) were divided randomly into 3 groups (n = 7 each): cannulation alone (sham group), CPB alone (control group), and CPB + MSC (MSC group). An experimental rat CPB model was established, and CPB was maintained for 30 minutes. In the MSC group, MSCs (1 × 106 cells) derived from the FM of ACI rats with a different major histocompatibility complex haplotype (RT-1a) were administrated intravenously before CPB initiation. Results Serum concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-1β in the MSC group were significantly lower compared with the control group after CPB. Similarly, mRNA expression of proinflammatory cytokines in the lung was lower in the MSC group. Allogeneic administration of FM-MSCs remarkably decreased the lung injury score, protected alveolar structure, inhibited neutrophil infiltration to the lung interstitium, and stimulated cytoprotective cytokine production in the lung. Conclusions Allogeneic transplantation of FM-MSCs may be a potent strategy to prevent CPB-induced systemic inflammation and acute lung injury by suppressing the expression of inflammatory cytokines and promoting protective factors in the lung.
KW - acute lung injury
KW - cardiopulmonary bypass
KW - lung protection
KW - mesenchymal stem cells
KW - systemic inflammation
UR - http://www.scopus.com/inward/record.url?scp=85013469048&partnerID=8YFLogxK
U2 - 10.1016/j.jtcvs.2016.10.014
DO - 10.1016/j.jtcvs.2016.10.014
M3 - Article
C2 - 27838010
AN - SCOPUS:85013469048
SN - 0022-5223
VL - 153
SP - 726
EP - 734
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 3
ER -