Autologous Peripheral Blood Mononuclear Cells as Treatment in Refractory Acute Respiratory Distress Syndrome

Respiration. 2015;90(6):481-492. doi: 10.1159/000441799. Epub 2015 Nov 28.

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.

Objectives: 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.

Publication types

  • Case Reports
  • Retracted Publication

MeSH terms

  • Cadherins / blood
  • Cytokines / blood
  • Down-Regulation
  • Erythropoietin / administration & dosage
  • Extracorporeal Membrane Oxygenation
  • Fatal Outcome
  • Humans
  • Leukocytes, Mononuclear / transplantation*
  • Male
  • MicroRNAs / blood
  • Multiple Organ Failure / etiology
  • Respiratory Distress Syndrome / therapy*
  • Snail Family Transcription Factors
  • Transcription Factors / blood
  • Transplantation, Autologous
  • Up-Regulation
  • Young Adult

Substances

  • Cadherins
  • Cytokines
  • MicroRNAs
  • Snail Family Transcription Factors
  • Transcription Factors
  • Erythropoietin