title: Autologous Peripheral Blood Mononuclear Cells as Treatment in Refractory Acute Respiratory Distress Syndrome.
abstract: BACKGROUND
  Acute 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.
  
  
  OBJECTIVE
  A male patient with severe ARDS showed no clinical improvement with conventional therapies. Hence, an emergent experimental intervention was performed.
  
  
  METHODS
  We performed intratracheal administration of autologous peripheral blood-derived mononuclear cells (PBMCs) and erythropoietin (EPO).
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Division of Ear, Nose and Throat, Advanced Center for Translational Regenerative Medicine, Department for Clinical Science, Intervention and Technology, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Philipp
authors.initials: P
authors.lastname: Jungebluth
authors.forename: Bernhard
authors.initials: B
authors.lastname: Holzgraefe
authors.forename: Mei Ling
authors.initials: ML
authors.lastname: Lim
authors.forename: Adil Doganay
authors.initials: AD
authors.lastname: Duru
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lundin
authors.forename: Nina
authors.initials: N
authors.lastname: Heldring
authors.forename: Oscar P B
authors.initials: OPB
authors.lastname: Wiklander
authors.forename: Joel Z
authors.initials: JZ
authors.lastname: Nordin
authors.forename: Michael
authors.initials: M
authors.lastname: Chrobok
authors.forename: Christoph
authors.initials: C
authors.lastname: Roderburg
authors.forename: Sebastian
authors.initials: S
authors.lastname: Sjöqvist
authors.forename: Björn
authors.initials: B
authors.lastname: Anderstam
authors.forename: Antonio
authors.initials: A
authors.lastname: Beltrán Rodríguez
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Haag
authors.forename: Ylva
authors.initials: Y
authors.lastname: Gustafsson
authors.forename: Katharina G
authors.initials: KG
authors.lastname: Roddewig
authors.forename: Petra
authors.initials: P
authors.lastname: Jones
authors.forename: Matthew J A
authors.initials: MJA
authors.lastname: Wood
authors.forename: Tom
authors.initials: T
authors.lastname: Luedde
authors.forename: Ana I
authors.initials: AI
authors.lastname: Teixeira
authors.forename: Ola
authors.initials: O
authors.lastname: Hermanson
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
authors.forename: Håkan
authors.initials: H
authors.lastname: Kalzén
authors.forename: Samir
authors.initials: S
authors.lastname: El Andaloussi
authors.forename: Evren
authors.initials: E
authors.lastname: Alici
authors.forename: Paolo
authors.initials: P
authors.lastname: Macchiarini
mesh_terms: D015820:Cadherins / Q000097:blood; D016207:Cytokines / Q000097:blood; D015536:Down-Regulation; D004921:Erythropoietin / Q000008:administration & dosage; D015199:Extracorporeal Membrane Oxygenation; D017809:Fatal Outcome; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D035683:MicroRNAs / Q000097:blood; D009102:Multiple Organ Failure / Q000209:etiology; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000097:blood; D014182:Transplantation, Autologous; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015820:Cadherins; D016207:Cytokines; D035683:MicroRNAs; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D004921:Erythropoietin