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Author Notes:

Corresponding author: Mauricio Rojas, Email: rojasm@upmc.edu.

MR and KLB conceived, interpreted and analyzed the data and drafted the manuscript.

RP and NT were responsible for swine experiments, collection and assembly of data.

CC and SI executed the ELISA and FACS assays and they did the expansion of swine adherent CD45neg and consequent data analysis and interpretation.

AS and AM made substantial contributions in the conception and design of the experiments and critically revised the content of the completely revised manuscript.

LM, MB and NC were responsible for tissue processing, staining and analysis.

All authors read and approved the final manuscript.

The authors declare that they have no competing interests.

Subjects:

Research Funding:

This research was supported by grant numbers 5P01 HL0669496-02, 5K01HL084683-02 and 1RO1HL083019-01 from the National Heart Lung and Blood Institute, a grant from the American Federation for Aging Research, Emory University URC #2003100 the McKelvey Center for Lung Transplantation at Emory University and the Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases at the University of Pittsburgh.

Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model

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Journal Title:

Stem Cell Research & Therapy

Volume:

Volume 4, Number 26

Publisher:

, Pages 1-12

Type of Work:

Article | Final Publisher PDF

Abstract:

Introduction: The acute respiratory distress syndrome (ARDS), affects up to 150,000 patients per year in the United States. We and other groups have demonstrated that bone marrow derived mesenchymal stromal stem cells prevent ARDS induced by systemic and local administration of endotoxin (lipopolysaccharide (LPS)) in mice. Methods: A study was undertaken to determine the effects of the diverse populations of bone marrow derived cells on the pathophysiology of ARDS, using a unique ex-vivo swine preparation, in which only the ventilated lung and the liver are perfused with autologous blood. Six experimental groups were designated as: 1) endotoxin alone, 2) endotoxin + total fresh whole bone marrow nuclear cells (BMC), 3) endotoxin + non-hematopoietic bone marrow cells (CD45 neg), 4) endotoxin + hematopoietic bone marrow cells (CD45 positive), 5) endotoxin + buffy coat and 6) endotoxin + in vitro expanded swine CD45 negative adherent allogeneic bone marrow cells (cultured CD45neg). We measured at different levels the biological consequences of the infusion of the different subsets of cells. The measured parameters were: pulmonary vascular resistance (PVR), gas exchange (PO2), lung edema (lung wet/dry weight), gene expression and serum concentrations of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6. Results: Infusion of freshly purified autologous total BMCs, as well as non-hematopoietic CD45(-) bone marrow cells significantly reduced endotoxin-induced pulmonary hypertension and hypoxemia and reduced the lung edema. Also, in the groups that received BMCs and cultured CD45neg we observed a decrease in the levels of IL-1β and TNF-α in plasma. Infusion of hematopoietic CD45(+) bone marrow cells or peripheral blood buffy coat cells did not protect against LPS-induced lung injury. Conclusions: We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS.

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© 2013 Rojas et al.; licensee BioMed Central Ltd.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 2.0 Generic License (http://creativecommons.org/licenses/by/2.0/).

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