Adipose-derived stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation

Abstract

BackgroundPulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, thus significantly increasing the mortality of burn patients. Adipose-derived stem cells (ASCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and ecfficacy of ASCs, in a well-characterized clinically relevant ovine model of ARDS.MethodsFemale sheep were surgically prepared. ARDS was induced by cooled cotton smoke inhalation. Following injury, sheep were ventilated, resuscitated with lactated Ringer’s solution, and cardiopulmonary hemodynamics were monitored for 48 hours in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring lung lymph flow, extravascular lung water content, protein content in plasma and lung lymph fluid. Sheep were randomly allocated to two groups: 1) ASCs: infused with 200 million of ASCs in 200mL of PlasmaLyteA starting 1 hours post-injury, n = 5; 2) control, treated with 200mL of PlasmaLyteA in a similar pattern, n = 5.ResultsLung lymph flow increased 9-fold in control sheep as compared to baseline. Protein in the plasma was significantly decreased, while it was increased in the lung lymph. The treatment with ASCs significantly attenuated these changes. Treatment with ASCs almost led to the reversal of increased pulmonary vascular permeability and lung water content. Pulmonary gas exchange was significantly improved by ASCs. Infusion of the ASCs did not negatively affect pulmonary artery pressure and other hemodynamic variables.ConclusionsASCs infusion was well tolerated. The results suggest that intravenous ASCs modulate pulmonary microvascular hyper-permeability and prevent the onset of ARDS in our experimental model.

Preclinical and clinical studies of smoke-inhalation-induced acute lung injury: update on both pathogenesis and innovative therapy

“…16,17 Substantial investigation has demonstrated that MSCs are beneficial for the treatment of ALI in preclinical models, including rodents and human tissues. 17,18 In addition, different sources of MSCs, including human amnion-derived MSCs, 19 adipose-derived stem cells, 20 bone-marrow MSCs (BMMSCs), 14,21,22 and nonmuscle myosin IIA-silenced BMMSCs (NM-IIA BMMSCs), 23 were effective in SI-ALI animal models (Table 1). The results of these studies showed that the wet/dry (W/D) ratio in lungs was significantly reduced, and partial pressure of oxygen (PaO 2 ) and the PaO 2 /FiO 2 ratio (where FiO 2 is the fraction of inspired oxygen) were significantly improved after delivery of MSCs.…”

Emerging therapies for smoke inhalation injury: a review

“…Treatment groups were noted to have improved pulmonary function demonstrated by improved PaO 2 /FiO 2 ratio, oxygenation index, and improved peak airway pressures. In addition, these animals also had improvement in the pulmonary microvascular hyperpermeability seen after smoke inhalation injury which was evident by decreased lung lymph flow and increased plasma protein levels when compared to control animals that did not receive stem cell therapy [19].…”

“…Ihara et al investigated the effect of adipose-derived mesenchymal stem cells on pulmonary microvascular changes using a sheep model of smoke inhalation injury [19]. Sheep were exposed to cotton smoke and then divided into groups that either received adipose-derived stem cells or a control vehicle.…”

Adipose-Derived Stromal/Stem Cells from Large Animal Models: from Basic to Applied Science

“…sheep and cattle) are limited. Of note, Ihara et al [52] used an ovine model of acute respiratory distress syndrome (ARDS) induced by smoke inhalation to estimate the efficacy of intravenously administrated ASCs. It has been shown that ASCs delivered at a dose of 2.0 × 10 8 cells, rem a r k a b l y r e d u c e d p u l m o n a r y m i c r o v a s c u l a r hyperpermeability, significantly ameliorating pulmonary gas exchange and improving the oxygenation index.…”