title: Intraperitoneal adoptive transfer of mesenchymal stem cells enhances recovery from acid aspiration acute lung injury in mice.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) might act as fine-tuners of inflammation during acute lung injury. We assessed the effects of adoptive transfer of MSCs in acid aspiration acute lung injury and explored the role of long pentraxin PTX3.
  
  
  METHODS
  We conducted a prospective experimental interventional study on wild-type (WT) and PTX3-deficient (PTX3-/-) mice. Acute lung injury was induced in WT and PTX3-/-mice by instillation of hydrochloric acid into the right bronchus. One hour later, animals received intraperitoneal sterile phosphate-buffered saline (PBS), WT-MSCs (1 × 106) or PTX3-/--MSCs (1 × 106). Twenty-four hours after injury, we measured the effects of treatments on arterial blood gases, wet/dry lung weight (W/D), CT scan analysis of lung collapse, neutrophils, TNFα and CXCL1 in bronchoalveolar lavage, and plasma PTX3. D-dimer was assayed in 1 week and OH-proline in 2 weeks to track the fibrotic evolution.
  
  
  RESULTS
  In 24 h, in comparison to PBS, WT-MSCs improved oxygenation and reduced W/D and alveolar collapse. These effects were associated with decreased concentrations of alveolar neutrophils and cytokines. WT-MSCs increased D-dimer concentration and decreased OH-proline levels, too. Treatment with PTX3-/--MSCs ameliorated oxygenation, W/D, and alveolar TNFα, though to a lesser extent than WT-MSCs. PTX3-/--MSCs did not improve lung collapse, neutrophil count, CXCL1, D-dimer, and OH-proline concentrations. The protective effects of WT-MSCs were dampened by lack of endogenous PTX3, too.
  
  
  CONCLUSIONS
  In acid aspiration acute lung injury, MSCs improve pulmonary function and limit fibrosis by fine-tuning inflammation. The role of PTX3 in determining MSCs' effects might merit further scrutiny.
authors.affiliation: Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mauri
authors.affiliation: School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Zambelli
authors.affiliation: Research Center 'M. Tettamanti', Fondazione MBBM/San Gerardo Hospital, Monza, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cappuzzello
authors.affiliation: School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bellani
authors.affiliation: Research Center 'M. Tettamanti', Fondazione MBBM/San Gerardo Hospital, Monza, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Dander
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, MI, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Sironi
authors.affiliation: Mouse and Animal Pathology Lab, Fondazione Filarete, Milan, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Castiglioni
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, MI, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Doni
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, MI, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.affiliation: School of Medicine and Surgery, University of Milan-Bicocca, Monza, Italy.|Research Center 'M. Tettamanti', Fondazione MBBM/San Gerardo Hospital, Monza, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.affiliation: Humanitas Clinical and Research Center, Rozzano, MI, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garlanda
authors.affiliation: Research Center 'M. Tettamanti', Fondazione MBBM/San Gerardo Hospital, Monza, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'amico
authors.affiliation: Department of Anesthesia, Critical Care and Emergency, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, 20122, Milan, Italy. antonio.pesenti@unimi.it.|Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. antonio.pesenti@unimi.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Pesenti
keywords: Acid aspiration syndrome; Acute lung injury; Acute respiratory distress syndrome; Pentraxin 3; Stem cells