Intrapulmonary autologous transplant of bone marrow-derived mesenchymal stromal cells improves lipopolysaccharide-induced acute respiratory distress syndrome in rabbit

Abstract

BackgroundLung diseases such as acute respiratory distress syndrome (ARDS) have a high incidence worldwide. The current drug therapies for ARDS have supportive effects, making them inefficient. New methods such as stromal cell therapy are needed for this problem.MethodsThis research was performed with ten New Zealand rabbits in two groups. Bone marrow aspiration was performed on the treated group, and mesenchymal stem cells were isolated and cultured. The experimental model of ARDS was induced using LPS from Escherichia coli strain O55:B5. Then, 1010 bone marrow mesenchymal stem cells (BM-MSCs) were autologously transplanted intrapulmonary in the treatment group, and 1–2 ml of PBS in the control group. The clinical signs, computed tomographic (CT) scans, echocardiography, blood gas analysis, complete blood count, and cytokine levels were measured before and at 3, 6, 12, 24, 48, 72, and 168 h after BM-MSC transplant. Finally, the rabbits were killed, and histopathological examination was performed.ResultsThe results showed that BM-MSCs decreased the severity of clinical symptoms, the number of white blood cells and heterophils in the blood, the total cell count, and number of heterophils and macrophages in bronchoalveolar lavage, and balanced the values of arterial blood gases (increase in partial pressure of oxygen and O2 saturation and decrease in the partial pressure of carbon dioxide). They also downregulated the tumor necrosis factor (TNF)-α and interleukin (IL)-6 concentrations and increased the IL-10 concentrations at different times compared with time 0 and in the control group, significantly. In the CT scan, a significant decrease in the Hounsfield units and total lung volume was found by echocardiography, and in comparing the two groups, a significant difference in the parameters was noticed. The histopathology demonstrated that the BM-MSCs were able to reduce the infiltration of inflammatory cells and pulmonary hemorrhage and edema.ConclusionsThis study indicated that BM-MSCs play a significant role in the repair of lung injury.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-2272-x) contains supplementary material, which is available to authorized users.

Mesenchymal stem/stromal cells: the therapeutic effects in animal models of acute pulmonary diseases

“…The results also show that the experimental model of the acute pulmonary inflammation peaks after infusion of infectious agents at 24-48 h. Accordingly, in a study by Mokhber Dezfouli et al, transplantation of stem/stromal cell was performed 24 h after inflammation with maximal inflammatory symptoms, in contrast to most of the studies that have performed stem/stromal cell transplantation between 30 min and 4 h after inflammation. Their results indicated the significant effects of MSCs on reducing inflammation and pulmonary edema, and improvement in clinical symptoms compared with control group [5].…”

“…Today, the MSCs-based cell therapy is a promising method for treatment of acute diseases of the lung. Regarding the nature and the ability of MSCs in secreting the different paracrine agents, such as growth factors, the endothelial and epithelial permeability regulatory factors and the anti-inflammatory cytokines are effective in the treatment of acute pulmonary disorders [4,5].…”

“…The recent studies have displayed the effects of paracrine in these cells, such as angiogenesis stimulation, adjustment of inflammatory conditions and immune responses in animal models of pulmonary diseases [27,28]. A new therapeutic strategy using MSCs causes the significant decline in the acute pulmonary inflammation induced by Lipopolysacaride (LPS) in the animal models of mice [27,28,30], rabbit [5] and sheep [31].…”

“…However, the available clinical data on the effects of the isolated MSCs from bone marrow is more than the other cells. The various reports indicate the efficacy of stem/stromal cell-based therapies in the significant reduction of the acute pulmonary inflammation induced by LPS in mice [28,30,47,48], rats [48][49][50], rabbit [5] and sheep [31], the pulmonary inflamma induced by oleic acid in rats [51] and pig [37], the lung inflammation caused by inhalation of smoke in sheep [36] and the inflammation of lung due to H9N2 avian influenza in mice [52] (Table 1).…”

“…Although both intrapulmonary and systemic transplantation of the isolated MSCs from bone marrow lead to decrement of mortality and inflammation and improvement of alveolar fluid clearance despite the minimal transplantation of stem/stromal cells in the lung [72], bone marrow mesenchymal stem/stromal cells (BM-MSCs) in the ARDS experimental model in rabbits [5] and BM-MSCs in the ARDS experimental model in sheep [31] is superior to intravenous transplantation.…”