title: Human mesenchymal stem cells attenuate early damage in a ventilated pig model of acute lung injury.
abstract: 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.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Department of Respiratory Medicine, Fiona Stanley Hospital, Murdoch, Western Australia, Australia; Stem Cell Unit, Institute for Respiratory Health, Nedlands, Western Australia, Australia. Electronic address: yuben.moodley@uwa.edu.au.
authors.forename: Yuben
authors.initials: Y
authors.lastname: Moodley
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Cell and Tissue Therapies WA, Royal Perth Hospital, Perth, Western Australia, Australia.
authors.forename: Marian
authors.initials: M
authors.lastname: Sturm
authors.affiliation: Cell and Tissue Therapies WA, Royal Perth Hospital, Perth, Western Australia, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Shaw
authors.affiliation: Department of Medicine, Pathology, and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Chiko
authors.initials: C
authors.lastname: Shimbori
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Nedlands, Western Australia, Australia; Stem Cell Unit, Institute for Respiratory Health, Nedlands, Western Australia, Australia.
authors.forename: Dino B A
authors.initials: DB
authors.lastname: Tan
authors.affiliation: Department of Medicine, Pathology, and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Kolb
authors.affiliation: Department of Anesthesia, University of Manitoba, Winnipeg, Canada.
authors.forename: Ruth
authors.initials: R
authors.lastname: Graham
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000628:therapy*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D006439:Hemodynamics; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019301:Oleic Acid / Q000633:toxicity; D012121:Respiration, Artificial / Q000009:adverse effects; D056152:Respiratory Rate; D013552:Swine
chemical_list: D016209:Interleukin-8; D016328:NF-kappa B; D016753:Interleukin-10; D019301:Oleic Acid
keywords: Acute lung injury (ALI); Mesenchymal stem cells (MSC); Nuclear factor-light chain enhancer of activated B cells (NF-κB); Oleic acid (OA); Pig