• Philipp Jungebluth, Bernhard Holzgraefe, Mei Ling Lim, Adil Doganay Duru, Vanessa Lundin, Nina Heldring, Oscar P B Wiklander, Joel Z Nordin, Michael Chrobok, Christoph Roderburg, Sebastian Sjöqvist, Björn Anderstam, Antonio Beltrán Rodríguez, Johannes C Haag, Ylva Gustafsson, Katharina G Roddewig, Petra Jones, Matthew J A Wood, Tom Luedde, Ana I Teixeira, Ola Hermanson, Ola Winqvist, Håkan Kalzén, Samir El Andaloussi, Evren Alici, and Paolo Macchiarini.
• Division of Ear, Nose and Throat, Advanced Center for Translational Regenerative Medicine, Department for Clinical Science, Intervention and Technology, Karolinska Institutet, Huddinge, Stockholm, Sweden.
• Respiration. 2015 Jan 1; 90 (6): 481-92.

BackgroundAcute respiratory distress syndrome (ARDS) is a devastating disorder. Despite enormous efforts in clinical research, effective treatment options are lacking, and mortality rates remain unacceptably high.ObjectivesA male patient with severe ARDS showed no clinical improvement with conventional therapies. Hence, an emergent experimental intervention was performed.MethodsWe performed intratracheal administration of autologous peripheral blood-derived mononuclear cells (PBMCs) and erythropoietin (EPO).ResultsWe found that after 2 days of initial PBMC/EPO application, lung function improved and extracorporeal membrane oxygenation (ECMO) support was reduced. Bronchoscopy and serum inflammatory markers revealed reduced inflammation. Additionally, serum concentration of miR-449a, b, c and miR-34a, a transient upregulation of E-cadherin and associated chromatin marks in PBMCs indicated airway epithelial differentiation. Extracellular vesicles from PBMCs demonstrated anti-inflammatory capacity in a TNF-α-mediated nuclear factor-x03BA;B in vitro assay. Despite improving respiratory function, the patient died of multisystem organ failure on day 38 of ECMO treatment.ConclusionsThis case report provides initial encouraging evidence to use locally instilled PBMC/EPO for treatment of severe refractory ARDS. The observed clinical improvement may partially be due to the anti-inflammatory effects of PBMC/EPO to promote tissue regeneration. Further studies are needed for more in-depth understanding of the underlying mechanisms of in vivo regeneration.© 2015 S. Karger AG, Basel.

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