Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury

• Published in: Stem cell research Vol. 17; no. 1; pp. 25 - 31
• Main Authors: Moodley, Yuben, Sturm, Marian, Shaw, Kathryn, Shimbori, Chiko, Tan, Dino B.A., Kolb, Martin, Graham, Ruth
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.07.2016; Elsevier
• Subjects: Acute lung injury (ALI); Acute Lung Injury - etiology; Acute Lung Injury - therapy; Animals; Cell Nucleus - metabolism; Disease Models, Animal; Hemodynamics; Humans; Interleukin-10 - metabolism; Interleukin-8 - metabolism; Lung - metabolism; Lung - pathology; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells (MSC); Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Microscopy, Fluorescence; Neutrophils - cytology; Neutrophils - immunology; Neutrophils - metabolism; NF-kappa B - metabolism; Nuclear factor-light chain enhancer of activated B cells (NF-κB); Oleic acid (OA); Oleic Acid - toxicity; Pig; Respiration, Artificial - adverse effects; Respiratory Rate; Swine; Oleic acid (OA); Acute lung injury (ALI); Mesenchymal stem cells (MSC); Nuclear factor-light chain enhancer of activated B cells (NF-κB); Pig
• ISSN: 1873-5061; 1876-7753
• DOI: 10.1016/j.scr.2016.05.005

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a major cause of global morbidity and mortality. Mesenchymal stem cells (MSC) have shown promise in treating inflammatory lung conditions. We hypothesised that human MSC (hMSC) can improve ALI/ARDS through their anti-inflammatory actions. We subjected pigs (n=6) to intravenous oleic acid (OA) injury, ventilation and hMSC infusion, while the controls (n=5) had intravenous OA, ventilation and an infusion vehicle control. hMSC were infused 1h after the administration of OA. The animals were monitored for additional 4h. Nuclear translocation of nuclear factor-light chain enhancer of activated B cells (NF-κB), a transcription factor that mediates several inflammatory pathways was reduced in hMSC treated pigs compared to controls (p=0.04). There was no significant difference in lung injury, assessed by histological scoring in hMSC treated pigs versus controls (p=0.063). There was no difference in neutrophil counts between hMSC-treated pigs and controls. Within 4h, there was no difference in the levels of IL-10 and IL-8 pre- and post-treatment with hMSC. In addition, there was no difference in hemodynamics, lung mechanics or arterial blood gases between hMSC treated animals and controls. Subsequent studies are required to determine if the observed decrease in inflammatory transcription factors will translate into improvement in inflammation and in physiological parameters over the long term. •Early effects of MSC in large animal models of ALI are rarely investigated.•Oleic acid-induced lung injuries in ventilated pigs were treated with MSC for 4h.•Nuclear translocation of NF-κB was lower in the lungs of hMSC-treated pigs than controls.•Slight reduction in lung injury was observed in hMSC-treated pigs versus controls.•Ventilator and physiological parameters did not differ after 4h of hMSC treatment.