Autologous transplantation of adipose-derived stromal cells combined with sevoflurane ameliorates acute lung injury induced by cecal ligation and puncture in rats

Abstract

Adipose-derived stromal cells (ADScs) have excellent capacities for regeneration and tissue protection, while sevoflurane, as a requisite component of surgical procedures, has shown therapeutic benefit in animal models of sepsis. This study therefore determined if the combination of sevoflurane and ADSCs exerted additional protective effects against acute lung injury (ALI) induced by cecal ligation and puncture (CLP) in rats. The animals were randomized into five groups: (sham operation (group I), CLP followed by mechanical ventilation (group II), CLP plus sevoflurane at 0.5 minimum alveolar concentration (group III), CLP plus intravenous autologous 5 × 10 6 ADScs (group iV), and CLP plus sevoflurane and ADSCs (group V). Levels of the pro-inflammatory cytokines tumor necrosis factor-α, transforming growth factor-β1, interleukin-1β and interleukin-6 were significantly increased in CLP rats. Moreover, epithelial sodium channel expression levels and activities of Na/K-ATPase and alveolar fluid clearance were significantly reduced in CLP-induced ALI rats. ADSCs improved all these parameters, and these effects were further enhanced by the addition of sevoflurane. In conclusion, combined treatment with ADSCs and sevoflurane is superior to either ADSCs or sevoflurane therapy alone for preventing ALI. This beneficial effect may be partly due to improved alveolar fluid clearance by the paracrine or systemic production of keratinocyte growth factor and via anti-inflammatory properties. Acute respiratory distress syndrome (ARDS) and its early stage, acute lung injury (ALI), represent a devastating clinical syndrome characterized by lung tissue edema and acute hypoxemic respiratory failure, finally leading to lung fibrogenesis. Despite extensive research efforts, mortality among critically ill patients remains high (about 40%) 1. Alveolar fluid clearance (AFC) is generally believed to be the main mechanism responsible for clearing edema fluid from airspaces into the lung interstitium 1. Sodium ions enter alveolar type II epithelial cells primarily through the epithelial sodium channel (ENaC) expressed at the apical surface, composed of α, β, and γ subunits, and are pumped out by Na/K-ATPase on the basolateral surface, driving osmotic water transport 2-4. However, AFC can be reduced by multiple pathways that impair ENaC and/or Na/K-ATPase, such as high tidal volume ventilation, hypoxia, and pro-inflammatory cytokines 5-7. Previous studies found that patients with ALI/ARDS were also characterized by reduced AFC. Clearance of excessive pulmonary edema is thus key to ensuring effective treatment and improving survival 8,9. Increasing numbers of in vivo experimental and preliminary clinical studies have identified mesenchymal stem cells (MSCs) as a promising therapy for various pulmonary diseases, including ALI 10-12. MSCs have the capacity to restore injured tissues by producing several growth factors, as well as immunomodulatory and open

Mir-204 Regulates LPS-Induced A549 Cell Damage by Targeting FOXK2

“…Hirsutanol A (HA) has a strong cytotoxic effect as a sessile mushroom compound. Studies have found that HA can induce tumor cell apoptosis by upregulating cleaved-caspase-3, but it is rarely reported in ALI and ARDS [ 6 , 7 ].…”

Topotecan reduces sepsis‐induced acute lung injury and decreases the inflammatory response via the inhibition of the NF‐κB signaling pathway

“…Moreover, previous studies have found that the lungs are relatively fragile organs and that 40% of ALI patients are caused by sepsis 9 . The cecal ligation puncture (CLP) model is widely used in exploring the treatment of sepsis, such as in studying the impact of different treatments on the survival rate of patients with sepsis 10 . However, the effect of TPT in the CLP model remains unknown.…”

“…9 The cecal ligation puncture (CLP) model is widely used in exploring the treatment of sepsis, such as in studying the impact of different treatments on the survival rate of patients with sepsis. 10 However, the effect of TPT in the CLP model remains unknown.…”